US7657385B2 - Structure-based hepatitis C virus drug design - Google Patents

Abstract

The extracellular loop of CD81 is a cellular receptor for the E2 protein of hepatitis C virus. A CD81 crystal structure has been elucidated and is provided for use in the structure-based design of compounds which bind to CD81 and thus block the binding of HCV. Methods such as docking and de novodrug design can be used.

Description

All documents cited herein are incorporated by reference in their entirety.

TECHNICAL FIELD

This invention is in the field of the use of structure-based drug design methods to identify compounds that bind to CD81, which is a cell-surface receptor for hepatitis C virus (HCV).

BACKGROUND ART

Chronic HCV infection occurs in about 3% of the world's population. It is a major cause of liver disease, but effective anti-HCV drugs are not yet available.

In October 1998, the extracellular loop of CD81 was reported as a cellular receptor for the E2 protein of HCV [1]. It is an object of the invention to facilitate rational structure-based drug design of chemical compounds that interact with CD81 to inhibit the binding of HCV.

DISCLOSURE OF THE INVENTION

The invention is based on the elucidation of a crystal structure for the large extracellular loop (LEL; amino acids 113-201) of human CD81. This facilitates structure-based design of compounds which bind to CD81 and thus block the binding of HCV.

The invention provides a computer-based method for identifying a ligand for CD81, comprising the steps of: (a) providing a 3D structural representation of the large extracellular loop of CD81 in a storage medium on a computer; and (b) using the computer to apply structure-based drug design techniques to the structural representation.

Structure-Based Drug Design Techniques

Structure-based drug design techniques can be applied to the structural representation of the LEL in order to identify compounds that interact with CD81 to block HCV binding. A variety of suitable techniques [e.g. ref. 2] are available to the skilled person.

Software packages for implementing molecular modelling techniques for use in structure-based drug design include SYBYL [3], AMBER [4], CERIUS² [5], INSIGHT II [5], CATALYST [5], QUANTA [5], HYPERCHEM [6], CHEMSITE [7] etc.

This software can be used to determine binding surfaces of the LEL in order to reveal features such as van der Waals contacts, electrostatic interactions, and/or hydrogen bonding opportunities. These binding surfaces may be used as follows:

Docking

Docking aligns the 3D structures of two or more molecules to predict the conformation of a complex formed from the molecules [e.g. ref 8]. According to the present invention, molecules are docked with the LEL structure to assess their ability to interact with CD81.

Docking can be accomplished by either geometric matching of the ligand and its receptor or by minimising the energy of interaction. Geometric matching algorithms are preferred because of their relative speed.

Suitable docking algorithms include, but are not limited to:

• • DOCK.[9], the prototypical program for structure-based drug design.
  • AUTODOCK [10, 4], which docks ligands in a flexible manner to receptors using grid-based Monte Carlo simulated annealing. The flexible nature of the AUTODOCK procedure helps to avoid bias (e.g. in orientation and conformation of the ligand in the active site) introduced by the user researcher [11] because, whilst the starting conformation in a rigid docking is normally biased towards an minimum energy conformation of the ligand, the binding conformation may be of relatively high conformational energy [12].
  • MOE-DOCK [13], in which a simulated annealing search algorithm is used to flexibly dock ligands. A grid-based energy evaluation is used to score docked conformations.
  • FLExX [3], which docks conformationally flexible ligands into a binding site using an incremental construction algorithm that builds the ligand in the site. Docked conformations are scored based on the strength of ligand-receptor interactions.
  • GOLD [14], a genetic algorithm for flexible ligand docking, with full ligand and partial protein flexibility. Energy functions are partly based on conformation and non-bonded contact information.
  • AFFINITY [5], which uses a two step process to dock ligands. First, initial placements of the ligand within the receptor are made using a Monte Carlo type procedure to search both conformational and Cartesian space. Second, a simulated annealing phase optimises the location of each ligand placement. During this phase, AFFINITY holds the ‘bulk’ of the receptor (atoms not in the binding site) rigid, while the binding site atoms and ligand atoms are movable.
  • C².LigandFit [5], which uses the energy of the ligand-receptor complex to automatically find best binding modes. Stochastic conformational search technique are used, and the best results from the conformational sampling are retained. A grid method is used to evaluate non-bonded interactions between the rigid receptor and the flexible ligand atoms.

Preferably, the docking algorithm is used, in a ‘high throughput’ mode, in which members of large structural libraries of potential ligands are screened against the receptor structure [15].

Suitable structural libraries include the ACD (Available Chemical Directory, from MDL Inc), AsInEx, Bionet, ComGenex, the Derwent World Drug Index (WDI), the Contact Service Company database, LaboTest, ChemBridge Express Pick, ChemStar, BioByteMasterFile, Orion, SALOR, TRIAD, ILIAD, the National Cancer Institute database (NCI), and the Aldrich, Fluka, Sigman and Maybridge catalogs. These are commercially available (e.g. the HTS Chemicals collections from Oxford Molecular, or the LeadQuest™ files from Tripos).

Pharmacophore hypotheses

A pharmacophore (i.e. a collection of chemical features and 3D constraints that expresses specific characteristics responsible for activity) can be defined for the LEL. The pharmacophore preferably includes surface-accessible features, more preferably including hydrogen bond donors and acceptors, charged/ionisable groups, and/or hydrophobic patches. These may be weighted depending on their relative importance in conferring activity [16].

Pharmacophores can be determined using software such as CATALYST (including HypoGen or HipHop) [5], CERIUS2, or constructed by hand from a known conformation of a lead compound. The pharmacophore can be used to screen structural libraries, using a program such as CATALYST [5]. The CLIX program [17] can also be used, which searches for orientations of candidate molecules in structural databases that yield maximum spatial coincidence with chemical groups which interact with the receptor.

de novo Compound Design

The binding surface or pharmacophore of the LEL can be used to map favourable interaction positions for functional groups (e.g. protons, hydroxyl groups, amine groups, hydrophobic groups and/or divalent cations) or small molecule fragments. Compounds can then be designed de novo in which the relevant functional groups are located in the correct spatial relationship to interact with CD81.

Once functional groups or small molecule fragments which can interact with specific sites in the CD81 binding surface have been identified, they can be linked in a single compound using either bridging fragments with the correct size and geometry or frameworks which can support the functional groups at favourable orientations, thereby providing a compound according to the invention. Whilst linking of functional groups in this way can be done manually, perhaps with the help of software such as QUANTA or SYBYL, automated or semi-automated de novo design approaches are also available:

• • MCDLNG [18], which fills a receptor binding site with a close-packed array of generic atoms and uses a Monte Carlo procedure to randomly vary atom types, positions, bonding arrangements and other properties.
  • MCSS/HOOK [19, 20, 5], which links multiple functional groups with molecular templates taken from a database.
  • LUDI [21, 5], which computes the points of interaction that would ideally be fulfilled by a ligand, places fragments in the binding site based on their ability to interact with the receptor, and then connects them to produce a ligand.
  • GROW [22], which starts with an initial ‘seed’ fragment (placed manually or automatically) and grows the ligand outwards.
  • SPROUT [23], suite which includes modules to: identify favourable hydrogen bonding and hydrophobic regions within a binding pocket (HIPPO module); select functional groups and position them at target sites to form starting fragments for structure generation (EleFAnT); generate skeletons that satisfy the steric constraints of the binding pocket by growing spacer fragments onto the start fragments and then connecting the resulting part skeletons (SPIDeR); substitute hetero atoms into the skeletons to generate molecules with the electrostatic properties that are complementary to those of the receptor site (MARABOU). The solutions can be clustered and scored using the ALLigaTOR module.
  • LEAPFROG [3], which evaluates ligands by making small stepwise structural changes and rapidly evaluating the binding energy of the new compound. Changes are kept or discarded based on the altered binding energy, and structures evolve to increase the interaction energy with the receptor.
  • GROUPBUILD [24], which uses a library of common organic templates and a complete empirical force field description of the non-bonding interactions between a ligand and receptor to construct ligands that have chemically reasonable structure and have steric and electrostatic properties complimentary to the receptor binding site.
  • CAVEAT [25], which designs linking units to constrain acyclic molecules.
  • RASSE [26]
    The LEL Binding Site

To simplify computational complexity, algorithms for docking and ligand design will typically focus only on the binding site of a receptor—it is pointless to attempt to dock a ligand with a region in the receptor which is known not to be involved. Binding site identification is included in some algorithms (e.g. C².LigandFit, the ‘Binding Site Analysis’ module of INSIGHT II, the SPHGEN routine of DOCK). Some manual guidance may be required (e.g. AFFINITY).

Where a binding site has to be defined for the CD81-LEL, this should include amino acid residue Phe186. It may also include one or more of Leu154, Thr163, Ile181, Ile182, Leu185, Glu188, and Asp196. The binding site may include the whole of helix D.

The Structural Representation

The invention involves the use of a 3D structural representation of the LEL. This may be a representation of (a) the complete LEL, (b) a fragment of CD81 that comprises the LEL, or (c) a fragment of the LEL which includes the amino acids which interact with HCV E2 protein.

The structural representation is preferably based on or derived from the atomic co-ordinates cd81lel.pdb as set out herein, which represents the LEL dimer [see also refs. 27, 28 & 29]. Suitable structural representations include 3D models and molecular surfaces derived from these atomic co-ordinates.

Variants of cd81lel.pdb can also be used for the invention, such as variants in which the r.m.s. deviation of the x, y and z co-ordinates for all heavy (i.e. not hydrogen) atoms are all less than 2.5 Å (e.g. less than 2 Å, preferably less than 1 Å, and more preferably less than 0.5 Å or less than 0.1 Å) compared with cd81lel.pdb. Co-ordinate transformations which retain the 3D spatial relationships of atoms may also be used to give suitable variants.

Preferred fragments of the LEL whose co-ordinates can be used in the invention include amino acid residue Phe186. The fragments may also include one or more of Leu154, Thr163, Ile181, Ile182, Leu185, Glu188, and Asp196.

It is preferred that the methods of the invention use only one protein chain i.e. only of the monomers in cd81lel.pdb. Where only one monomer is used, it is preferred to use the first monomer (residues 113-202) rather than the second (residues 213-302).

The water molecules in cd81lel.pdb can optionally be omitted when performing the methods of the invention.

The atomic co-ordinates given herein can also be used as the basis of models of further protein structures. For example, a homology model could be based on the LEL structure of the present invention. The co-ordinates can also be used in the solution or refinement of further crystal structures of CD81.

The Storage Medium

The storage medium in which the LEL structural representation is provided is preferably random-access memory (RAM), but may also be read-only memory (ROM e.g. CDROM), or a diskette. The storage medium may be local to the computer, or may be remote (e.g. a networked storage medium, including the internet).

The invention also provides a computer-readable medium for a computer, characterised in that the medium contains atomic co-ordinates and/or a 3D structural representation of the LEL of CD81. The atomic co-ordinates are preferably cd81lel.pdb or variants thereof.

Any suitable computer can be used in the present invention.

Testing Compounds

The methods may comprise the further steps of: (c) providing a compound identified by said structure-based drug design techniques; and (d) contacting said compound with CD81, or a fragment thereof containing the LEL, and assaying the interaction between them.

The assay may be of a competitive nature. For example, the assay may include HCV E2 protein (either purified, or in the context of the HCV virion), such that E2 and the compound compete for binding to CD81.

Compounds and Their Uses

The methods of the invention identify compounds that can interact with CD81. These compounds may be designed de novo, may be known compounds, or may be based on known compounds. The compounds may be useful pharmaceuticals themselves, or may be prototypes which can be used for further pharmaceutical refinement (i.e. lead compounds) in order to improve binding affinity or other pharmacologically important features (e.g. bio-availability, toxicology, metabolism, pharmacokinetics etc.).

The invention thus provides: (i) a compound identified using the methods of the invention; (ii) a compound identified using the methods of the invention for use as a pharmaceutical; (iii) the use of a compound identified using the methods of the invention in the manufacture of a medicament for treating hepatitis C infection; and (iv) a method of treating a patient with hepatitis C infection, comprising administering an effective amount of a compound identified using the methods of the invention.

These compounds preferably interact with CD81 with a binding constant in the micromolar or, more preferably, nanomolar range or stronger.

As well as being useful compounds individually, ligands identified in silico by the structure-based design techniques can also be used to suggest libraries of compounds for ‘traditional’ in vitro or in vivo screening methods. Important pharmaceutical motifs in the ligands can be identified and mimicked in compound libraries (e.g. combinatorial libraries) for screening for CD81-binding activity.

Crystals

The invention also provides a composition comprising an extracellular region (e.g. the LEL) of CD81 in crystalline form. The crystal can be used for diffraction studies e.g. X-ray or neutron diffraction.

The crystal is preferably in the monoclinic space group P2₁ (a=31.5 Å, b=77.2 Å, c=38.5 Å, β=107.4°), with two molecules per asymmetric unit (Vm of 2.16 ų/dalton).

In some embodiments, the composition may include ligands which are co-crystallised with the CD81 fragment; in other embodiments the composition may be essentially pure protein.

BRIEF DESCRIPTION OF DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

FIG. 1 shows: (1A) the CD81-LEL isolated chain tertiary structure, highlighting the head domain localisation relative to the N- and C-terminal helices (α-helices A and E, respectively), and the labelling of secondary structure elements. The two disulphide bridges are shown by yellow bonds; (1B) the dimeric CD81-LEL, showing the two subunits in blue and purple, with the helix labels distinguished by a symbol. The molecular two-fold axis is close to vertical, and located between the N- and C-termini of the two chains. Solid dots in the purple subunit trace an approximate path for the loops not observable in the electron density maps. (1C) A GRASP view of the molecular surface of the CD81-LEL dimer, in an orientation corresponding that of the blue subunit in panel 1A. This orientation brings α-helices C and D in the foreground; they can be recognised by comparison to panel A and by the low polarity region (white colour) in the upper part of the molecular surface.

FIG. 2 shows an amino acid sequence alignment of LEL segments from mammalian CD81 and other tetraspanins. A symbol indicating the secondary structure [PROCHECK, ref. 30; H=α-helix; G=3₁₀ helix) is shown on the top line. On the leftmost column, name and organism are indicated. The accession numbers for the sequences used in the alignment are: human CD81, NP_—004347; Saguinus oedipus, CAB89875; rat, NP_—037219; mouse, P35762; human CD9, NP_—001760; human TSPAN2, NP_—005716; mouse CD53, NP 031677; human CD82, NP_—002222; human CD63, NP_—001771; human TALLA1, AAF4412; human NET4, AAC17120. Amino acid sequences of CD81 from chimpanzee, green monkey, and hamster have been obtained from ref. 1. The last four sequences contain insertions which have not been included in the alignment to avoid the introduction of long gaps, located between pairs of underlined residues. In detail, the insertion stretches are: in CD82 eLMNRPEVTy and sLSVRKGFCEAPGNRTQSGNHPEDWPv; in CD63, dWEKPs, cINVTVGc and kAi; in TALLA1, sPYFLEh, cMNETDc and tVAATKVNq; in NET4, aFGADDWNLNIYFNt and dVINTQCGYDARQKPEVDQQIv. The conserved Cys residues are enclosed in yellow boxes. Amino acids involved in the association interface are shown in pink boxes. The residues which are different between hCD81-LEL and agmCD81-LEL or tamCD81-LEL are marked in green or blue, respectively. Note that residue 163 is mutated in agmCD81-LEL and in tamCD81-LEL.

FIG. 3 shows: (3A) a schematic view of the location of Cys156--Cys190 and Cys157--Cys175 disulphide bridges (yellow bonds) within the head domain of CD81-LEL. The additional residues displayed are the sites of mutation observed in AGM CD81-LEL (green) and in tamarin CD81-LEL (red); (3B) the residues surrounding Tyr127, the head domain core, including electron density for the two disulphide bridges; (3C) a molecular surface representation of the CD81-LEL dimer, showing mutation sites 163, 186 and 196 (green patches) which have been shown to affect binding to HCV E2. Phe196 is in the upper-right part of the figure.

MODES FOR CARRYING OUT THE INVENTION

CD81-LEL Production

CD81-LEL was purified from a recombinant E. coli strain as a fusion protein with the IgG binding domain of the S. aureus protein A. After purification of the chimeric protein, CD81-LEL was separated from the fusion by specific protease cleavage and further purified for the crystallization experiments. The purified protein was fully active as judged by the recombinant E2/CD81 inhibition of binding assay [1].

CD81-LEL Crystallisation

Crystals of CD81-LEL were obtained by mixing purified CD81-LEL at 10 mg/mil with 0.1M MES buffer (pH 6.0), 0.1M sodium chloride, and 10% PEG4000. The crystals belong to the monoclinic space group P2₁ (a=31.5 Å, b=77.2 Å, c=38.5 Å, β=107.4°), with two molecules per asymmetric unit (Vm of 2.16 ų/dalton). Crystals were flash-cooled at 100K with addition of 20% glycerol as cryoprotectant.

Whilst native crystals could be obtained easily, it was difficult to obtain suitable heavy atom derivatives for multiple isomorphous replacement techniques.

Three suitable derivatives were eventually produced, based on Lu, Hg and Pt:

Parameter	Native 1	LuCl3	Hg(Ac)2	K2PtCl6	Native 2

Diffraction data
Wavelength (Å)	1.54	1.54	1.54	1.54	0.93
Resolution (Å)	2.7	2.7	3.0	3.3	1.6
Unique reflections	5136	4979	3619	2521	21557
Rmerge (%)	5.8	6.0	8.4	4.4	3.8
Completeness (%)	99.7	98.0	98.1	91.8	98.0
	(99.4)	(93.4)	(97.1)	(87.5)	(93.1)
Redundancy	3.4	2.0	3.2	8.2	6.9
MIR phasing
Phasing power/Rcullis
(acentric)		1.49/0.78	1.25/0.84	1.30/0.87
(centric)		1.16/0.82	0.98/0.85	0.90/0.89
(anom)		0.95/0.97	0.66/0.99	0.65/0.99

Overall FOM (acentric/centric)	0.63/0.58
Refinement

Resolution range					20.0-1.6
Rfactor/Rfree (%)					18.7/23.8
No. of protein atoms					1345
No. of solvent atoms					194
Ramachandran distribution
% core					92.4
% allowed					7.6
% generous					0.0
% disallowed					0.0
r.m.s. bonds (Å)					0.006
r.m.s. angles (°)					1.2
Average B values (Å2)					35.2
NB:
Rmerge = Σl Ii − <Ii> l/Σ <Ii>, where Ii is the observed intensity and <Ii> is the average intensity over symmetry equivalent measurements.
Phasing power = Σ |FHl/Σ | |FPH(obs)l − lFPH(calc)l l, where FPH and FH are the derivative and calculated heavy-atom structure factors, respectively.
Rcullis = Σ | |FPH − FPl − lFH(calc)l/lFPH − FP|, where FPH, FP and FH are the derivative, native and calculated heavy-atom structure factors, respectively.
Rfactor = Σ lFobsl − lFcalc| |/Σ |Fobsl, Rfree is the same as Rfactor, but for a 5% subset of all reflections that were never used in crystallographic refinement.
FOM (FIG. of merit) = lF(hkl)best/lF(hkl)l
Completeness is reported for all reflection and for the highest resolution shell.

Diffraction and Structure Solving

Native and derivative diffraction data were collected in house. Additional native data (at 1.6 Å resolution) were collected on beamline ID14 (ESRF, Grenoble, France), on a MAR CCD detector. All data were processed using DENZO and SCALEPACK [31] and merged using the CCP4 program suite [32]. Crystallographic phases were calculated with CCP4 programs and refined using SHARP [33] and SOLOMON [34]. The resulting electron density maps allowed about 80% of the two independent molecules to be traced. Model building and inspection was based on the O suite [35]. The structure was refined using CNS [36] and REFMAC [37]0.5% of the unique data were used to monitor the free R-factor. The final values for general R-factor and free R-factor are 18.7% and 23.8%, respectively. The refined model consists of 176 amino acids, with 194 water molecules, at 1.60 Å resolution. No residues are found in disallowed regions of the Ramachandran plot. Residues 238-241 are disordered in a A′B′loop.

Analysis of the Crystal Structure

FIG. 1A shows the CD81-LEL tertiary structure, which is essentially composed of five α-helices (A, B, C, D, E) spanning residues Asn115-Asp137, Ala140-Asp155, Leu165-Asn172, Asn180-Phe186 and Asp189-Gly200, respectively (amino acids numbered according to the full CD81 sequence; refs 38 & 39). A short 3₁₀ helical segment covers residues Leu162-Ala164. The anti-parallel A- and E-helices can be seen as the stalk of a mushroom-shaped molecule, whose head domain (about 60 residues) is built by packing of the shorter B-, C- and D-helices and their intervening loops (loops are defined by the helices they connect i.e. AB, . . . , DE). A DALI search [40] of 3D protein structures did not show significant structural homology of the CD81-LEL fold to any known protein tertiary structure.

The dimeric assembly observed in the crystallographic asymmetric unit is shown in FIG. 1B. Two CD81-LEL chains assemble around a local two-fold axis, displaying intermolecular contacts mainly at the A:A′ helix interface (a ′ symbol distinguishes features of the partner subunit) and along the B-helix, which is in contact with the C-terminal region of the facing protomer. The subunit interface (986 Ų) is composed of apolar residues for about 70% of its contact region.

The A:A′ interface segment involves primarily residues Val114, Ile119, Val123, Gln125, Phe126 and Gln129, in both antiparallel helices, together with solvent mediated interactions between exposed polar side chains at the rim of the contact region. The second interface region includes residues Asn142, Val146, Thr149, Phe150, Thr153 & Leu154 which contact Leu197′, Phe198′, Ser199′ & Gly200′. No water molecules are buried at the association interface.

Bivalent molecules (such as specific antibodies) capable of recognising human CD81 have been reported to have a higher affinity than E2 for CD81 [41]. In agreement with the crystal structure, this suggests that CD81 exists as a homodimeric species at the cell surface. In the crystal structure, the distance between the D- and D′-helices is about 30 Å, close to the distance between antigen-binding sites in an assembled antibody molecule.

The C-terminal His-tag does not appear to have a structural influence because the proximity of N- and C-termini within each chain, permitted by the antiparallel arrangement of A- and E-helices, is compatible with their topological location between TM3 and TM4 of native CD81 [39]. Moreover, due to the quaternary structure two-fold symmetry, the N- and C-termini of the two protomers fall in a restricted area, but on opposite faces of the assembled dimer (FIG. 1B). This quaternary organization is compatible with inter- and intra-cellular aggregation of CD81 in homo-dimeric species, through the association interface described.

The overall shape of the CD81-LEL dimer is further characterized in FIG. 1C, as a surface displaying electrostatic potential. Besides the localization of negative potential in the central region of the dimer, a low polarity patch is present in a surface region comprising the C- and D-helices. In the crystal packing this region is virtually solvent inaccessible, due to extended contacts with a symmetry equivalent dimer.

The CD81-LEL head domain is essentially composed of the last two turns of the A-helix, the B-, C-, D-helices, the intervening segments, and the DE loop. The domain fold is firstly stabilized by two tetraspanin-invariant intramolecular disulfide bridges [1, 38, 39, 41], which originate from two adjacent Cys residues (156 & 157) and are oriented approximately in opposite directions within the head domain (FIG. 3A). Their topological connections are Cys156--Cys190 and Cys157--Cys175: the first involves residues located at the C-terminus of the B-helix (Cys156) and at the N-terminus of the E-helix (Cys190); the second connects the BC segment (Cys157) with the CD loop region (Cys175). The latter region is fully exposed to solvent and specifically kinked towards the head domain core by virtue of the Cys157—Cys175 bridge. Of the four Cys residues, only Cys 175 is partly accessible to solvent (20 Ų).

The head domain is built around the core residue Tyr127, fully buried and surrounded by Leu131, Va147, Phe150, His151 and by the. Asp128--His191 hydrogen-bonded salt-bridge. Tyr127 OH atom is hydrogen-bonded to His151 NE2 atom (2.7 Å) and is 3.61 Å from the Cys190Sγ atom (FIG. 3B). The imidazole ring of His151 is nestled between the two disulfide bridges, and is at hydrogen-bonding distance from Cys190 Sγ (3.56 Å). A hydrogen-bonding network involving Tyr127, His151 and Cys190 may play a role in regulating the redox properties of one or both disulfide bridges. Tyr127 is strictly conserved between species in CD81 (FIG. 2), and in all the CD9 sequences known to date; residue 191 is either His or Gln in amino acid sequences representing different tetraspanin sub-families (FIG. 2).

Sequence database surveys show that the tetraspanin family is composed of several sub-families (CD9, CD37, CD63, CD53, CD82, CD151 and others; ref. 38), for a total of about 160 amino acid sequences currently recognized. Among these, CD81 and CD9 families display close sequence (and thus structural) homology (23% residue identities are observed between human CD81-LEL and human CD9-LEL). FIG. 2 shows multiple amino acid sequence alignments of CD81-LEL from seven different species, together with human CD9-LEL and other tetraspanins. Sequence-based dendrogram analysis indicates that, within the sequences included in FIG. 2, human CD82-LEL is the one most distantly related to CD81-LEL (only 9% identical residues).

Besides the clearly recognized tetraspanin four-Cys consensus motif, inspection of the CD81 and CD9 alignment in FIG. 2 shows strict residue conservation at thirteen residues. Among these, four are charged amino acids (Lys116, Asp117, Lys148, and Lys201), which are totally solvent exposed in the assembled CD81-LEL dimer. The remaining nine conserved residues can be divided into three structural classes:

• (a) Tyr127, His151 and Ile194 are buried residues involved in intramolecular interactions stabilizing the head domain and its contacts to the E-helix, as described above.
• (b) Val123, Phe126, Leu154 and Phe198, which are primarily involved in subunit interface contacts, together with residues Ile119 and Phe150, conservatively substituted at the association interface. Conservation of the interface hydrophobic residues can be recognized throughout the sequence alignment of FIG. 2, suggesting that the observed subunit interface has a general functional significance for both homo- or hetero-dimeric tetraspanin association related to intra- or inter-cellular recognition processes.
• (c) Gly158 and Pro176, both of which display unique positions and conformations (as indicated by their Ramachandran Φ,Ψ pairs) within the head domain fold, occurring after the Cys156-Cys157 pair and after Cys175. The selection of Gly and Pro at sites 158 and 176, respectively, may be required by the structural constraints imposed on the CD loop by the Cys157-Cys175 bridge, coding its specific kink towards the B-helix.

Analysis of the available sequences indicates that tetraspanin LEL segments display enhanced residue variability, deletions or insertions in the protein segments 158-174 and 176-189, which are comprised between the two disulfide bridges (see FIG. 2). The two segments span the BC loop, the C- and the D-helices and the DE hinge i.e. mostly solvent-exposed regions of the head domain (see FIGS. 1B & 3A). The structural location and sequence variability of this protein region, as opposed to generally conserved protein interface and core regions, suggests its involvement in species- or tetraspanin-specific recognition processes.

No binding of the HCV E2 glycoprotein to african green monkey (Chlorocebus aethiops) CD81 has been observed, but the LELs of human and AGM CD81 differ at only five residues: 154, 163, 186, 188 and 197 [1]. Conversely, E2 does bind to tamarin (Saguinus oedipus) CD81 with high affinity, and it differs from human CD81 only at residues 155, 163, 169, 180 and 196. Three of the AGM mutations have been engineered into human CD81-LEL and their binding properties versus recombinant E2 and anti-CD81 antibodies have been analysed in vitro [41]. Phe186 is the most critical residue affecting E2 binding, since the F186A mutation in human CD81-LEL fully impairs binding to E2 and to specific antibodies, the introduction of Phe186 in AGM CD81-LEL restores E2 binding, and tamarin CD81 displays Phe186 [1, 41, 42]. The Thr163Ala mutation marginally improves human CD81 binding to E2, whereas Asp196Glu mutation decreases binding to E2 [41].

From a structural viewpoint, the tamarin and AGM mutated residues map in the head domain, with the exception of residues 196 and 197, which fall next to the C-terminus (see FIG. 3C), Leu197 being a subunit interface residue in human CD81. Residues 155, 163, 180, 186 and 188 are solvent exposed, such that their conservative substitution should not affect the domain conformation. On the other hand, the substitution of residues 154 and 169 is subject to polarity and residue size restrictions, since they occur at buried locations next to both disulfide bridges. In human CD81 Thr163 is located in the short 3₁₀ segment preceding the C-helix, and Phe186 is the last residue in the D-helix. The two antiparallel helices build up a sort of narrow “canyon” sub-structure, whose floor is essentially defined by the Cys157--Cys175 disulfide connecting the CD loop to the domain core. Residues 163 and 186 are located at the canyon end opposing the CD loop (FIGS. 3A & 3C).

The mutant AGM and tamarin residues which affect E2 binding map to the C-, D-, E-helices, and the intervening segments i.e. residues mostly comprised within the two conserved disulfide bridges and including the 179-193 sequence stretch recognised as the minimal epitope for E2 binding [41]. Conformational integrity of this region is likely related to the oxidised state of the disulfide bridges, particularly the Cys157-Cys175 bridge; reduction of the disulfides impairs E2 and antibody recognition experiments [41, 43]. Sequence alignments show that the identified region displays highest residue variability within the CD81-LEL subfamily (FIG. 2), but also within other members of the tetraspanin family, which may bear specific residue deletions and insertions affecting the tertiary structure according to their molecular recognition requirements.

The conservation in the CD81 sequences of the hydrophobic residues Ile181, Ile182, Leu185, and Phe186 belonging to the D-helix (FIG. 2) is peculiar, since their solvent-exposed location (FIGS. 1C & 3A) should select against their conservation through species. Such an uncommon structural property, the extended intermolecular crystal contacts observed in this region, and the dramatic loss of E2 affinity related to Phe86 mutation, suggest that the D-helix region is the docking site for the viral glycoprotein E2.

It will be understood that the invention has been described by way of example only and modifications may be made whilst remaining within the scope and spirit of the invention.

REFERENCES (THE CONTENTS OF WHICH ARE HEREBY INCORPORATED IN FULL HEREIN)

• 1—Pileri et al. (1998) Science 282:938-941.
• 2—Further details: Rational drug design: novel methodology and practical applications, ACS Symposium Series vol. 719 (Parrill & Reddy eds., 1991).
• 3—Available from Tripos Inc (http://www.tripos.com).
• 4—Available from Oxford Molecular (http://www.oxmol.co.uk/).
• 5—Available from Molecular Simulations Inc (http://www.msi.com/).
• 6—Available from Hypercube Inc (http://www.hyper.com/).
• 7—Available from Pyramid Learning (http://www.chemsite.org/).
• 8—Blaney & Dixon (1993) Perspectives in Drug Discovery and Design 1:301
• 9—Kuntz et al. (1982) J. Mol. Biol. 161:269-288); available from UCSF.
• 10—Goodsell & Olson (1990) Proteins: Structure, Function and Genetics 8:195-202.
• 11—Meyer et al. (1995) Persp. Drug Disc. Des. 3:168-195
• 12—Nicklaus et al. (1995) Bioorganic & Medicinal Chemistry 3:411
• 13—Available from Chemical Computing Group Inc. (http://www.chemcomp.com/).
• 14—Jones et al. (1997) J. Mol. Biol. 267:727-748
• 15—Martin (1992) J. Med. Chem. 35:2145-54.
• 16—also Computer-Assisted Lead Finding and Optimization (eds. Testra & Folkers, 1997).
• 17—Davic & Lawrence (1992) Proteins 12:31-41.
• 18—Gehlhaar et al. (1995) J. Med. Chem. 38:466-72.
• 19—Caflish et al. (1993) J. Med. Chem. 36:2142-67
• 20—Eisen et al. (1994) Proteins: Str. Funct. Genet. 19:199-221.
• 21—Böhm (1992) J. Comp. Aided Molec. Design 6:61-78.
• 22—Moon & Howe (1991) Proteins: Str. Funct. Genet. 11:314-328.
• 23—Available from http://chem.leeds.ac.uk/ICAMS/SPROUT.html.
• 24—Rotstein et al. (1993) J. Med. Client. 36:1700.
• 25—Lauri & Bartlett (1994) Comp. Aided Mol. Design 8:51-66.
• 26—Lai (1996) J. Chem. Inf. Comput. Sci. 36:1187-1194.
• 27—File 1G8Q at the Protein Data Bank [http://www.rcsb.org/pdb/]
• 28—Kitadokoro et al. (2001) Acta Crystallogr D Biol Crstallogr 57:156-158.
• 29—Kitadokoro et al. (2001) EMBO J. 20:12-18.
• 30—Laskowski et al. (1993) J. Appl. Crystallogr. 26:283
• 31—Otwinowski & Minor (1996) Methods Enzymol. 276:307.
• 32—CCP4, Acta Crystallogr. D50, 760 (1994).
• 33—Fortelle &. Bricogne (1997) Methods Enzymol. B 472
• 34—Abrahams & Leslie (1996) Acta Crystallogr. D52, 30.
• 35—Jones et al. (1991) Acta Crystallogr. A47, 110
• 36—Brunget et al. (1998) Acta Crystallogr. D 54, 905
• 37—Murshudov et al. (1997) Acta Crystallogr. D 53, 240
• 38—Maecker et al. (1997) FASEB J. 11:428-42.
• 39—Levy et al. (1998) Annu Rev Immunol. 16:89-109
• 40—Holm & Sander (1993) J. Mol. Biol. 233, 123
• 41—Higginbottom et al. (2000) J. Virol. 74:3642-9.
• 42—Meola et al. (2000) J. Virol. 74:5933.
• 43—Petracca et al. (2000) J. Virol. 74:4824-30.

PDB FILE LISTING −cd81lel.pdb

REMARK	Written by O version 7.0.0
REMARK	Mon Jun 26 07:13:19 2000

CRYST1

31.485

77.172

38.462

90.00

107.39

90.00

ORIGX1	1.000000	0.000000	0.000000		0.00000
ORIGX2	0.000000	1.000000	0.000000		0.00000
ORIGX3	0.000000	0.000000	1.000000		0.00000
SCALE1	0.031761	−0.000001	0.009946		0.00000
SCALE2	0.000000	0.012958	0.000000		0.00000
SCALE3	0.000000	0.000000	0.027245		0.00000

ATOM	1	CB	PHE	A	113	13.054	44.460	−4.086	1.00	35.22	6
ATOM	2	CG	PHE	A	113	13.550	44.904	−5.447	1.00	34.10	6
ATOM	3	CD1	PHE	A	113	13.436	46.217	−5.867	1.00	33.03	6
ATOM	4	CD2	PHE	A	113	14.097	43.957	−6.288	1.00	31.53	6
ATOM	5	CE1	PHE	A	113	13.846	46.604	−7.112	1.00	41.68	6
ATOM	6	CE2	PHE	A	113	14.536	44.353	−7.552	1.00	33.43	6
ATOM	7	CZ	PHE	A	113	14.417	45.655	−7.929	1.00	29.35	6
ATOM	8	C	PHE	A	113	13.055	44.591	−1.648	1.00	34.73	6
ATOM	9	O	PHE	A	113	13.493	43.601	−1.095	1.00	35.94	8
ATOM	10	N	PHE	A	113	15.194	44.738	−2.818	1.00	38.93	7
ATOM	11	CA	PHE	A	113	13.749	45.121	−2.929	1.00	35.51	6
ATOM	12	N	VAL	A	114	12.014	45.304	−1.292	1.00	30.69	7
ATOM	13	CA	VAL	A	114	11.297	44.908	−0.047	1.00	30.59	6
ATOM	14	CB	VAL	A	114	10.318	46.078	0.218	1.00	28.83	6
ATOM	15	CG1	VAL	A	114	9.273	45.698	1.249	1.00	39.07	6
ATOM	16	CG2	VAL	A	114	11.101	47.339	0.495	1.00	32.04	6
ATOM	17	C	VAL	A	114	10.519	43.644	−0.291	1.00	33.72	6
ATOM	18	O	VAL	A	114	9.766	43.438	−1.254	1.00	38.10	8
ATOM	19	N	ASN	A	115	10.631	42.726	0.661	1.00	26.02	7
ATOM	20	CA	ASN	A	115	9.999	41.431	0.616	1.00	26.31	6
ATOM	21	CB	ASN	A	115	11.119	40.392	0.761	1.00	32.36	6
ATOM	22	CG	ASN	A	115	10.695	38.985	0.416	1.00	36.81	6
ATOM	23	OD1	ASN	A	115	9.539	38.606	0.608	1.00	37.44	8
ATOM	24	ND2	ASN	A	115	11.665	38.213	−0.109	1.00	41.24	7
ATOM	25	C	ASN	A	115	9.050	41.307	1.840	1.00	29.28	6
ATOM	26	O	ASN	A	115	9.588	40.946	2.886	1.00	29.32	8
ATOM	27	N	LYS	A	116	7.818	41.715	1.661	1.00	28.31	7
ATOM	28	CA	LYS	A	116	6.877	41.671	2.790	1.00	30.52	6
ATOM	29	CB	LYS	A	116	5.534	42.201	2.323	1.00	32.42	6
ATOM	30	CG	LYS	A	116	4.438	42.302	3.360	1.00	40.71	6
ATOM	31	CD	LYS	A	116	3.494	41.125	3.184	1.00	54.74	6
ATOM	32	CE	LYS	A	116	2.097	41.504	3.656	1.00	50.77	6
ATOM	33	NZ	LYS	A	116	1.233	40.305	3.663	1.00	45.99	7
ATOM	34	C	LYS	A	116	6.740	40.325	3.467	1.00	29.54	6
ATOM	35	O	LYS	A	116	6.720	40.232	4.696	1.00	27.76	8
ATOM	36	N	ASP	A	117	6.611	39.248	2.695	1.00	29.77	7
ATOM	37	CA	ASP	A	117	6.551	37.911	3.304	1.00	30.69	6
ATOM	38	CB	ASP	A	117	6.396	36.802	2.261	1.00	35.31	6
ATOM	39	CG	ASP	A	117	5.055	36.833	1.558	1.00	41.21	6
ATOM	40	OD1	ASP	A	117	4.955	36.192	0.472	1.00	44.39	8
ATOM	41	OD2	ASP	A	117	4.140	37.496	2.092	1.00	44.63	8
ATOM	42	C	ASP	A	117	7.800	37.628	4.109	1.00	31.27	6
ATOM	43	O	ASP	A	117	7.612	37.076	5.208	1.00	29.68	8
ATOM	44	N	GLN	A	118	9.006	37.962	3.675	1.00	27.32	7
ATOM	45	CA	GLN	A	118	10.192	37.645	4.471	1.00	23.79	6
ATOM	46	CB	GLN	A	118	11.500	37.816	3.709	1.00	33.42	6
ATOM	47	CG	GLN	A	118	12.392	36.592	3.917	1.00	50.37	6
ATOM	48	CD	GLN	A	118	11.870	35.402	3.136	1.00	55.11	6
ATOM	49	OE1	GLN	A	118	11.385	34.436	3.730	1.00	61.81	8
ATOM	50	NE2	GLN	A	118	11.933	35.435	1.806	1.00	55.23	7
ATOM	51	C	GLN	A	118	10.218	38.513	5.755	1.00	25.07	6
ATOM	52	O	GLN	A	118	10.575	38.027	6.842	1.00	28.38	8
ATOM	53	N	ILE	A	119	9.863	39.760	5.566	1.00	25.14	7
ATOM	54	CA	ILE	A	119	9.880	40.701	6.719	1.00	23.26	6
ATOM	55	CB	ILE	A	119	9.498	42.128	6.266	1.00	27.36	6
ATOM	56	CG2	ILE	A	119	9.266	43.023	7.510	1.00	23.47	6
ATOM	57	CG1	ILE	A	119	10.560	42.718	5.345	1.00	30.01	6
ATOM	58	CD1	ILE	A	119	10.193	44.009	4.618	1.00	30.66	6
ATOM	59	C	ILE	A	119	8.938	40.184	7.788	1.00	23.31	6
ATOM	60	O	ILE	A	119	9.311	40.183	8.996	1.00	25.16	8
ATOM	61	N	ALA	A	120	7.712	39.788	7.412	1.00	24.17	7
ATOM	62	CA	ALA	A	120	6.781	39.316	8.463	1.00	25.04	6
ATOM	63	CB	ALA	A	120	5.384	38.976	7.916	1.00	29.48	6
ATOM	64	C	ALA	A	120	7.304	38.051	9.147	1.00	24.84	6
ATOM	65	O	ALA	A	120	7.234	37.964	10.377	1.00	25.63	8
ATOM	66	N	LYS	A	121	7.886	37.145	8.333	1.00	25.80	7
ATOM	67	CA	LYS	A	121	8.459	35.934	8.924	1.00	27.45	6
ATOM	68	CB	LYS	A	121	8.937	35.072	7.739	1.00	31.96	6
ATOM	69	CG	LYS	A	121	10.222	34.305	7.934	1.00	45.25	6
ATOM	70	CD	LYS	A	121	11.443	35.174	7.733	1.00	55.59	6
ATOM	71	CE	LYS	A	121	12.488	34.542	6.833	1.00	54.95	6
ATOM	72	NZ	LYS	A	121	13.434	35.534	6.259	1.00	49.41	7
ATOM	73	C	LYS	A	121	9.581	36.310	9.886	1.00	24.12	6
ATOM	74	O	LYS	A	121	9.630	35.792	11.038	1.00	26.90	8
ATOM	75	N	ASP	A	122	10.378	37.296	9.562	1.00	23.49	7
ATOM	76	CA	ASP	A	122	11.489	37.734	10.391	1.00	24.47	6
ATOM	77	CB	ASP	A	122	12.549	38.580	9.737	1.00	22.87	6
ATOM	78	CG	ASP	A	122	13.362	37.819	8.674	1.00	26.68	6
ATOM	79	OD1	ASP	A	122	13.273	36.574	8.574	1.00	32.55	8
ATOM	80	OD2	ASP	A	122	14.103	38.528	7.955	1.00	31.33	8
ATOM	81	C	ASP	A	122	10.982	38.456	11.665	1.00	24.38	6
ATOM	82	O	ASP	A	122	11.555	38.251	12.733	1.00	22.88	8
ATOM	83	N	VAL	A	123	9.945	39.256	11.552	1.00	24.91	7
ATOM	84	CA	VAL	A	123	9.363	39.886	12.747	1.00	22.20	6
ATOM	85	CB	VAL	A	123	8.288	40.939	12.399	1.00	18.76	6
ATOM	86	CG1	VAL	A	123	7.800	41.562	13.705	1.00	20.06	6
ATOM	87	CG2	VAL	A	123	9.037	42.026	11.568	1.00	23.40	6
ATOM	88	C	VAL	A	123	8.825	38.829	13.692	1.00	20.54	6
ATOM	89	O	VAL	A	123	9.008	38.889	14.911	1.00	22.54	8
ATOM	90	N	LYS	A	124	8.098	37.844	13.114	1.00	21.95	7
ATOM	91	CA	LYS	A	124	7.566	36.768	14.018	1.00	24.00	6
ATOM	92	CB	LYS	A	124	6.797	35.783	13.134	1.00	26.02	6
ATOM	93	CG	LYS	A	124	5.505	36.413	12.619	1.00	25.26	6
ATOM	94	CD	LYS	A	124	4.836	35.414	11.667	1.00	29.55	6
ATOM	95	CE	LYS	A	124	3.735	36.131	10.886	1.00	32.92	6
ATOM	96	NZ	LYS	A	124	3.115	35.139	9.941	1.00	31.45	7
ATOM	97	C	LYS	A	124	8.722	36.046	14.715	1.00	25.01	6
ATOM	98	O	LYS	A	124	8.678	35.783	15.931	1.00	24.77	8
ATOM	99	N	GLN	A	125	9.817	35.779	14.045	1.00	22.22	7
ATOM	100	CA	GLN	A	125	10.963	35.105	14.630	1.00	25.09	6
ATOM	101	CB	GLN	A	125	11.933	34.615	13.553	1.00	28.89	6
ATOM	102	CG	GLN	A	125	13.031	33.781	14.176	1.00	28.74	6
ATOM	103	CD	GLN	A	125	12.610	32.683	15.121	1.00	51.08	6
ATOM	104	OE1	GLN	A	125	11.475	32.201	15.227	1.00	48.79	8
ATOM	105	NE2	GLN	A	125	13.577	32.195	15.910	1.00	55.92	7
ATOM	106	C	GLN	A	125	11.677	35.939	15.667	1.00	22.42	6
ATOM	107	O	GLN	A	125	12.007	35.481	16.740	1.00	26.28	8
ATOM	108	N	PHE	A	126	11.872	37.249	15.396	1.00	21.19	7
ATOM	109	CA	PHE	A	126	12.395	38.149	16.407	1.00	23.84	6
ATOM	110	CB	PHE	A	126	12.358	39.571	15.868	1.00	20.40	6
ATOM	111	CG	PHE	A	126	12.978	40.587	16.762	1.00	22.25	6
ATOM	112	CD1	PHE	A	126	14.372	40.659	16.802	1.00	24.92	6
ATOM	113	CD2	PHE	A	126	12.201	41.422	17.567	1.00	24.93	6
ATOM	114	CE1	PHE	A	126	14.990	41.588	17.628	1.00	28.09	6
ATOM	115	CE2	PHE	A	126	12.844	42.353	18.368	1.00	21.69	6
ATOM	116	CZ	PHE	A	126	14.202	42.409	18.427	1.00	27.78	6
ATOM	117	C	PHE	A	126	11.592	38.131	17.688	1.00	21.94	6
ATOM	118	O	PHE	A	126	12.060	38.065	18.810	1.00	22.84	8
ATOM	119	N	TYR	A	127	10.246	38.180	17.534	1.00	19.86	7
ATOM	120	CA	TYR	A	127	9.349	38.135	18.698	1.00	20.03	6
ATOM	121	CB	TYR	A	127	7.865	38.224	18.184	1.00	23.84	6
ATOM	122	CG	TYR	A	127	6.918	37.987	19.351	1.00	21.94	6
ATOM	123	CD1	TYR	A	127	6.577	38.925	20.305	1.00	21.20	6
ATOM	124	CE1	TYR	A	127	5.735	38.634	21.368	1.00	17.80	6
ATOM	125	CD2	TYR	A	127	6.394	36.687	19.461	1.00	21.35	6
ATOM	126	CE2	TYR	A	127	5.542	36.351	20.521	1.00	23.38	6
ATOM	127	CZ	TYR	A	127	5.221	37.318	21.444	1.00	22.17	6
ATOM	128	OH	TYR	A	127	4.376	36.942	22.471	1.00	22.46	8
ATOM	129	C	TYR	A	127	9.552	36.818	19.437	1.00	18.72	6
ATOM	130	O	TYR	A	127	9.655	36.851	20.694	1.00	21.79	8
ATOM	131	N	ASP	A	128	9.606	35.711	18.693	1.00	23.27	7
ATOM	132	CA	ASP	A	128	9.726	34.407	19.418	1.00	22.55	6
ATOM	133	CB	ASP	A	128	9.674	33.283	18.359	1.00	25.98	6
ATOM	134	CG	ASP	A	128	8.249	33.014	17.910	1.00	29.92	6
ATOM	135	OD1	ASP	A	128	8.110	32.180	16.988	1.00	32.49	8
ATOM	136	OD2	ASP	A	128	7.294	33.586	18.464	1.00	27.69	8
ATOM	137	C	ASP	A	128	11.093	34.278	20.077	1.00	24.19	6
ATOM	138	O	ASP	A	128	11.158	33.755	21.208	1.00	22.87	8
ATOM	139	N	GLN	A	129	12.140	34.817	19.447	1.00	22.82	7
ATOM	140	CA	GLN	A	129	13.441	34.812	20.158	1.00	22.77	6
ATOM	141	CB	GLN	A	129	14.505	35.588	19.324	1.00	25.03	6
ATOM	142	CG	GLN	A	129	14.771	34.862	18.042	1.00	25.57	6
ATOM	143	CD	GLN	A	129	15.665	35.668	17.072	1.00	26.40	6
ATOM	144	OE1	GLN	A	129	15.978	35.087	16.038	1.00	30.69	8
ATOM	145	NE2	GLN	A	129	15.991	36.913	17.459	1.00	30.93	7
ATOM	146	C	GLN	A	129	13.299	35.632	21.434	1.00	22.40	6
ATOM	147	O	GLN	A	129	13.819	35.202	22.487	1.00	25.02	8
ATOM	148	N	ALA	A	130	12.695	36.829	22.395	1.00	20.16	7
ATOM	149	CA	ALA	A	130	12.602	37.564	22.647	1.00	19.19	6
ATOM	150	CB	ALA	A	130	12.049	39.003	22.397	1.00	21.18	6
ATOM	151	C	ALA	A	130	11.791	36.880	23.687	1.00	22.54	6
ATOM	152	O	ALA	A	130	12.047	36.945	24.912	1.00	22.88	8
ATOM	153	N	LEU	A	131	10.655	36.253	23.276	1.00	18.79	7
ATOM	154	CA	LEU	A	131	9.742	35.645	24.266	1.00	21.57	6
ATOM	155	CB	LEU	A	131	8.492	35.127	23.523	1.00	21.87	6
ATOM	156	CG	LEU	A	131	7.340	34.780	24.516	1.00	26.58	6
ATOM	157	CD1	LEU	A	131	6.825	36.097	25.128	1.00	24.19	6
ATOM	158	CD2	LEU	A	131	6.209	34.116	23.747	1.00	23.85	6
ATOM	159	C	LEU	A	131	10.454	34.451	24.948	1.00	21.60	6
ATOM	160	O	LEU	A	131	10.320	34.274	26.150	1.00	22.16	8
ATOM	161	N	GLN	A	132	11.181	33.692	24.137	1.00	22.17	7
ATOM	162	CA	GLN	A	132	11.884	32.531	24.707	1.00	23.12	6
ATOM	163	CB	GLN	A	132	12.508	31.669	23.581	1.00	22.76	6
ATOM	164	CG	GLN	A	132	11.381	30.963	22.796	1.00	24.05	6
ATOM	165	CD	GLN	A	132	11.961	30.193	21.606	1.00	25.65	6
ATOM	166	OE1	GLN	A	132	11.936	28.946	21.582	1.00	28.29	8
ATOM	167	NE2	GLN	A	132	12.428	30.852	20.541	1.00	25.24	7
ATOM	168	C	GLN	A	132	12.922	32.987	25.692	1.00	22.26	6
ATOM	169	O	GLN	A	132	13.006	32.389	26.770	1.00	23.25	8
ATOM	170	N	GLN	A	133	13.693	34.050	25.412	1.00	21.14	7
ATOM	171	CA	GLN	A	133	14.711	34.509	26.348	1.00	21.05	6
ATOM	172	CB	GLN	A	133	15.533	35.610	25.619	1.00	22.48	6
ATOM	173	CG	GLN	A	133	16.687	35.994	26.548	1.00	25.57	6
ATOM	174	CD	GLN	A	133	17.650	36.993	25.926	1.00	23.61	6
ATOM	175	OE1	GLN	A	133	17.463	37.432	24.806	1.00	28.80	8
ATOM	176	NE2	GLN	A	133	18.726	37.251	26.669	1.00	29.55	7
ATOM	177	C	GLN	A	133	14.070	35.146	27.572	1.00	22.02	6
ATOM	178	O	GLN	A	133	14.481	34.985	28.734	1.00	24.53	8
ATOM	179	N	ALA	A	134	12.946	35.879	27.368	1.00	22.25	7
ATOM	180	CA	ALA	A	134	12.270	36.531	28.489	1.00	24.32	6
ATOM	181	CB	ALA	A	134	11.058	37.332	27.987	1.00	24.55	6
ATOM	182	C	ALA	A	134	11.798	35.628	29.623	1.00	23.77	6
ATOM	183	O	ALA	A	134	11.708	35.947	30.819	1.00	27.92	8
ATOM	184	N	VAL	A	135	11.447	34.399	29.250	1.00	22.81	7
ATOM	185	CA	VAL	A	135	10.918	33.425	30.203	1.00	22.24	6
ATOM	186	CB	VAL	A	135	9.948	32.446	29.546	1.00	31.11	6
ATOM	187	CG1	VAL	A	135	8.682	33.122	29.084	1.00	29.66	6
ATOM	188	CG2	VAL	A	135	10.546	31.496	28.557	1.00	45.64	6
ATOM	189	C	VAL	A	135	12.043	32.676	30.843	1.00	25.73	6
ATOM	190	O	VAL	A	135	11.880	32.216	31.986	1.00	31.63	8
ATOM	191	N	VAL	A	136	13.147	32.472	30.135	1.00	30.36	7
ATOM	192	CA	VAL	A	136	14.211	31.649	30.768	1.00	29.23	6
ATOM	193	CB	VAL	A	136	14.704	30.717	29.663	1.00	30.54	6
ATOM	194	CG1	VAL	A	136	15.653	31.427	28.727	1.00	28.12	6
ATOM	195	CG2	VAL	A	136	15.237	29.401	30.184	1.00	33.07	6
ATOM	196	C	VAL	A	136	15.274	32.433	31.445	1.00	32.01	6
ATOM	197	O	VAL	A	136	16.080	31.921	32.242	1.00	35.58	8
ATOM	198	N	ASP	A	137	15.520	33.683	31.050	1.00	29.34	7
ATOM	199	CA	ASP	A	137	16.647	34.496	31.487	1.00	30.00	6
ATOM	200	CB	ASP	A	137	17.273	35.171	30.263	1.00	31.01	6
ATOM	201	CG	ASP	A	137	18.536	35.952	30.547	1.00	38.12	6
ATOM	202	OD1	ASP	A	137	19.181	36.426	29.580	1.00	33.65	8
ATOM	203	OD2	ASP	A	137	18.933	36.171	31.710	1.00	34.77	8
ATOM	204	C	ASP	A	137	16.127	35.551	32.450	1.00	35.73	6
ATOM	205	O	ASP	A	137	15.411	36.471	32.043	1.00	35.33	8
ATOM	206	N	ASP	A	138	16.486	35.444	33.718	1.00	41.35	7
ATOM	207	CA	ASP	A	138	16.026	36.345	34.735	1.00	44.53	6
ATOM	208	CB	ASP	A	138	16.349	35.881	36.159	1.00	55.88	6
ATOM	209	CG	ASP	A	138	14.551	35.422	36.525	0.00	27.18	6
ATOM	210	OD1	ASP	A	138	14.174	34.275	36.165	0.00	27.18	8
ATOM	211	OD2	ASP	A	138	13.773	36.235	37.082	0.00	27.18	8
ATOM	212	C	ASP	A	138	16.457	37.783	34.550	1.00	45.63	6
ATOM	213	O	ASP	A	138	15.642	38.619	34.905	1.00	46.37	8
ATOM	214	N	ASP	A	139	17.659	38.047	34.046	1.00	47.04	7
ATOM	215	CA	ASP	A	139	18.045	39.434	33.860	1.00	47.12	6
ATOM	216	CB	ASP	A	139	19.315	39.889	34.534	1.00	59.30	6
ATOM	217	CG	ASP	A	139	20.138	38.776	35.141	1.00	60.21	6
ATOM	218	OD1	ASP	A	139	20.667	37.956	34.371	1.00	66.48	8
ATOM	219	OD2	ASP	A	139	20.245	38.739	36.381	1.00	60.42	8
ATOM	220	C	ASP	A	139	17.980	39.852	32.397	1.00	44.11	6
ATOM	221	O	ASP	A	139	18.684	40.814	32.054	1.00	45.91	8
ATOM	222	N	ALA	A	140	17.165	39.159	31.588	1.00	36.40	7
ATOM	223	CA	ALA	A	140	17.097	39.640	30.176	1.00	34.34	6
ATOM	224	CB	ALA	A	140	16.549	38.514	29.305	1.00	29.85	6
ATOM	225	C	ALA	A	140	16.124	40.801	30.144	1.00	29.56	6
ATOM	226	O	ALA	A	140	14.956	40.665	29.725	1.00	28.22	8
ATOM	227	N	ASN	A	141	16.528	41.977	30.625	1.00	29.81	7
ATOM	228	CA	ASN	A	141	15.623	43.101	30.725	1.00	30.52	6
ATOM	229	CB	ASN	A	141	16.336	44.264	31.435	1.00	37.01	6
ATOM	230	CG	ASN	A	141	16.696	43.864	32.857	1.00	54.30	6
ATOM	231	OD1	ASN	A	141	15.795	43.768	33.690	1.00	48.05	8
ATOM	232	ND2	ASN	A	141	17.991	43.645	33.062	1.00	56.03	7
ATOM	233	C	ASN	A	141	15.225	43.622	29.319	1.00	25.07	6
ATOM	234	O	ASN	A	141	14.036	43.975	29.220	1.00	30.82	8
ATOM	235	N	ASN	A	142	16.189	43.580	28.407	1.00	32.80	7
ATOM	236	CA	ASN	A	142	15.802	44.039	27.068	1.00	27.52	6
ATOM	237	CB	ASN	A	142	16.955	44.259	26.125	1.00	32.75	6
ATOM	238	CG	ASN	A	142	17.649	45.601	26.305	1.00	52.93	6
ATOM	239	OD1	ASN	A	142	18.857	45.697	26.058	1.00	59.14	8
ATOM	240	ND2	ASN	A	142	16.922	46.626	26.735	1.00	57.80	7
ATOM	241	C	ASN	A	142	14.791	43.064	26.464	1.00	25.36	6
ATOM	242	O	ASN	A	142	13.788	43.551	25.878	1.00	26.29	8
ATOM	243	N	ALA	A	143	15.035	41.759	26.593	1.00	23.53	7
ATOM	244	CA	ALA	A	143	14.041	40.835	26.012	1.00	25.47	6
ATOM	245	CB	ALA	A	143	14.443	39.375	26.206	1.00	22.30	6
ATOM	246	C	ALA	A	143	12.661	41.003	26.568	1.00	24.29	6
ATOM	247	O	ALA	A	143	11.612	40.989	25.897	1.00	22.58	8
ATOM	248	N	LYS	A	144	12.519	41.185	27.922	1.00	21.87	7
ATOM	249	CA	LYS	A	144	11.258	41.408	28.541	1.00	20.70	6
ATOM	250	CB	LYS	A	144	11.375	41.391	30.083	1.00	28.64	6
ATOM	251	CG	LYS	A	144	11.856	40.022	30.597	1.00	26.79	6
ATOM	252	CD	LYS	A	144	12.210	40.226	32.089	1.00	31.38	6
ATOM	253	CE	LYS	A	144	13.007	39.023	32.585	1.00	45.61	6
ATOM	254	NZ	LYS	A	144	12.035	37.945	32.966	1.00	43.86	7
ATOM	255	C	LYS	A	144	10.663	42.717	28.045	1.00	19.65	6
ATOM	256	O	LYS	A	144	9.472	42.704	27.782	1.00	24.45	8
ATOM	257	N	ALA	A	145	11.500	43.758	27.888	1.00	22.72	7
ATOM	258	CA	ALA	A	145	10.889	45.019	27.383	1.00	24.10	6
ATOM	259	CB	ALA	A	145	11.949	46.097	27.451	1.00	23.70	6
ATOM	260	C	ALA	A	145	10.430	44.868	25.914	1.00	21.09	6
ATOM	261	O	ALA	A	145	9.302	45.355	25.644	1.00	21.56	8
ATOM	262	N	VAL	A	146	12.171	44.078	25.189	1.00	22.29	7
ATOM	263	CA	VAL	A	146	10.683	43.855	23.784	1.00	20.84	6
ATOM	264	CB	VAL	A	146	11.731	43.079	22.976	1.00	22.15	6
ATOM	265	CG1	VAL	A	146	11.112	42.478	21.711	1.00	23.27	6
ATOM	266	CG2	VAL	A	146	12.898	44.014	22.734	1.00	22.16	6
ATOM	267	C	VAL	A	146	9.361	43.149	23.742	1.00	19.58	6
ATOM	268	O	VAL	A	146	8.394	43.563	23.088	1.00	21.79	8
ATOM	269	N	VAL	A	147	9.239	42.066	24.552	1.00	19.17	7
ATOM	270	CA	VAL	A	147	7.968	41.312	24.548	1.00	19.64	6
ATOM	271	CB	VAL	A	147	8.263	40.138	25.586	1.00	23.25	6
ATOM	272	CG1	VAL	A	147	7.102	39.633	26.344	1.00	36.08	6
ATOM	273	CG2	VAL	A	147	8.943	39.101	24.664	1.00	32.42	6
ATOM	274	C	VAL	A	147	6.844	42.194	25.068	1.00	20.95	6
ATOM	275	O	VAL	A	147	5.742	42.204	24.529	1.00	21.71	8
ATOM	276	N	LYS	A	148	7.072	42.924	26.178	1.00	19.59	7
ATOM	277	CA	LYS	A	148	5.979	43.783	26.688	1.00	21.04	6
ATOM	278	CB	LYS	A	148	6.499	44.431	27.981	1.00	26.20	6
ATOM	279	CG	LYS	A	148	6.574	43.388	29.093	1.00	27.82	6
ATOM	280	CD	LYS	A	148	6.786	44.057	30.419	1.00	30.78	6
ATOM	281	CE	LYS	A	148	8.007	44.919	30.523	1.00	46.34	6
ATOM	282	NZ	LYS	A	148	8.210	45.450	31.917	1.00	44.31	7
ATOM	283	C	LYS	A	148	5.564	44.894	25.702	1.00	20.08	6
ATOM	284	O	LYS	A	148	4.365	45.111	25.584	1.00	23.45	8
ATOM	285	N	THR	A	149	6.509	45.375	24.919	1.00	22.66	7
ATOM	286	CA	THR	A	149	6.199	46.426	23.955	1.00	24.54	6
ATOM	287	CB	THR	A	149	7.501	46.993	23.359	1.00	28.59	6
ATOM	288	OG1	THR	A	149	8.175	47.743	24.398	1.00	27.03	8
ATOM	289	CG2	THR	A	149	7.137	47.974	22.239	1.00	26.03	6
ATOM	290	C	THR	A	149	5.444	45.829	22.784	1.00	22.31	6
ATOM	291	O	THR	A	149	4.445	46.365	22.357	1.00	23.09	8
ATOM	292	N	PHE	A	150	5.840	44.627	22.338	1.00	20.35	7
ATOM	293	CA	PHE	A	150	5.032	43.967	21.295	1.00	20.84	6
ATOM	294	CB	PHE	A	150	5.656	42.622	20.813	1.00	19.43	6
ATOM	295	CG	PHE	A	150	6.572	42.840	19.638	1.00	19.28	6
ATOM	296	CD1	PHE	A	150	7.767	43.517	19.804	1.00	23.21	6
ATOM	297	CD2	PHE	A	150	6.223	42.279	18.424	1.00	22.14	6
ATOM	298	CE1	PHE	A	150	8.628	43.662	18.709	1.00	24.38	6
ATOM	299	CE2	PHE	A	150	7.090	42.460	17.318	1.00	26.48	6
ATOM	300	CZ	PHE	A	150	8.274	43.138	17.487	1.00	26.64	6
ATOM	301	C	PHE	A	150	3.639	43.730	21.816	1.00	21.43	6
ATOM	302	O	PHE	A	150	2.641	43.978	21.161	1.00	22.18	8
ATOM	303	N	HIS	A	151	3.492	43.160	23.052	1.00	19.41	7
ATOM	304	CA	HIS	A	151	2.136	42.899	23.534	1.00	20.29	6
ATOM	305	CB	HIS	A	151	2.327	42.196	24.892	1.00	20.50	6
ATOM	306	CG	HIS	A	151	2.926	40.818	24.756	1.00	19.00	6
ATOM	307	CD2	HIS	A	151	3.109	39.943	23.786	1.00	21.53	6
ATOM	308	ND1	HIS	A	151	3.430	40.277	25.923	1.00	24.13	7
ATOM	309	CE1	HIS	A	151	3.844	39.057	25.645	1.00	22.94	6
ATOM	310	NE2	HIS	A	151	3.714	38.809	24.336	1.00	23.76	7
ATOM	311	C	HIS	A	151	1.264	44.140	23.689	1.00	17.69	6
ATOM	312	O	HIS	A	151	0.092	44.031	23.367	1.00	20.84	8
ATOM	313	N	GLU	A	152	1.799	45.257	24.154	1.00	20.91	7
ATOM	314	CA	GLU	A	152	0.990	46.458	24.397	1.00	21.45	6
ATOM	315	CB	GLU	A	152	1.887	47.401	25.181	1.00	24.45	6
ATOM	316	CG	GLU	A	152	1.146	48.737	25.465	1.00	35.51	6
ATOM	317	CD	GLU	A	152	1.910	49.450	26.575	1.00	37.49	6
ATOM	318	OE1	GLU	A	152	3.012	49.946	26.243	1.00	60.98	8
ATOM	319	OE2	GLU	A	152	1.409	49.523	27.706	1.00	54.52	8
ATOM	320	C	GLU	A	152	0.652	47.073	23.016	1.00	24.93	6
ATOM	321	O	GLU	A	152	−0.516	47.374	22.677	1.00	26.68	8
ATOM	322	N	THR	A	153	1.679	47.050	22.170	1.00	22.06	7
ATOM	323	CA	THR	A	153	1.553	47.631	20.837	1.00	23.76	6
ATOM	324	CB	THR	A	153	2.877	47.930	20.167	1.00	22.41	6
ATOM	325	OG1	THR	A	153	3.719	48.778	20.982	1.00	25.19	8
ATOM	326	CG2	THR	A	153	2.706	48.553	18.778	1.00	26.00	6
ATOM	327	C	THR	A	153	0.543	46.956	19.957	1.00	25.16	6
ATOM	328	O	THR	A	153	−0.255	47.624	19.292	1.00	27.39	8
ATOM	329	N	LEU	A	154	0.581	45.631	19.880	1.00	24.12	7
ATOM	330	CA	LEU	A	154	−0.293	44.865	19.028	1.00	24.17	6
ATOM	331	CB	LEU	A	154	0.475	43.699	18.382	1.00	24.04	6
ATOM	332	CG	LEU	A	154	1.735	44.158	17.692	1.00	23.64	6
ATOM	333	CD1	LEU	A	154	2.505	42.926	17.202	1.00	28.71	6
ATOM	334	CD2	LEU	A	154	1.410	45.020	16.462	1.00	27.37	6
ATOM	335	C	LEU	A	154	−1.519	44.271	19.703	1.00	25.12	6
ATOM	336	O	LEU	A	154	−2.253	43.539	19.036	1.00	30.55	8
ATOM	337	N	ASP	A	155	−1.650	44.490	20.998	1.00	24.04	7
ATOM	338	CA	ASP	A	155	−2.798	43.983	21.753	1.00	26.79	6
ATOM	339	CB	ASP	A	155	−4.088	44.595	21.191	1.00	29.32	6
ATOM	340	CG	ASP	A	155	−5.288	44.195	22.049	1.00	54.63	6
ATOM	341	OD1	ASP	A	155	−6.418	44.190	21.500	1.00	39.24	8
ATOM	342	OD2	ASP	A	155	−5.082	43.899	23.250	1.00	34.92	8
ATOM	343	C	ASP	A	155	−2.830	42.462	21.694	1.00	30.04	6
ATOM	344	O	ASP	A	155	−3.750	41.884	21.134	1.00	29.77	8
ATOM	345	N	CYS	A	156	−1.738	41.816	22.153	1.00	25.38	7
ATOM	346	CA	CYS	A	156	−1.681	40.340	22.082	1.00	25.86	6
ATOM	347	C	CYS	A	156	−0.797	39.854	23.234	1.00	26.35	6
ATOM	348	O	CYS	A	156	−0.269	40.677	24.000	1.00	26.19	8
ATOM	349	CB	CYS	A	156	−1.078	39.839	20.742	1.00	27.96	6
ATOM	350	SG	CYS	A	156	0.624	40.419	20.466	1.00	24.36	16
ATOM	351	N	CYS	A	157	−0.843	38.518	23.399	1.00	26.36	7
ATOM	352	CA	CYS	A	157	−0.036	37.954	24.518	1.00	27.31	6
ATOM	353	C	CYS	A	157	0.314	36.526	24.086	1.00	24.36	6
ATOM	354	O	CYS	A	157	−0.521	35.614	23.957	1.00	27.45	8
ATOM	355	CB	CYS	A	157	−0.965	37.922	25.747	1.00	33.17	6
ATOM	356	SG	CYS	A	157	−0.201	37.056	27.129	1.00	32.57	16
ATOM	357	N	GLY	A	158	1.578	36.266	23.759	1.00	23.62	7
ATOM	358	CA	GLY	A	158	1.997	34.967	23.282	1.00	23.46	6
ATOM	359	C	GLY	A	158	1.882	34.721	21.802	1.00	24.98	6
ATOM	360	O	GLY	A	158	1.347	35.496	21.016	1.00	30.72	8
ATOM	361	N	SER	A	159	2.419	33.571	21.340	1.00	23.28	7
ATOM	362	CA	SER	A	159	2.365	33.214	19.927	1.00	25.33	6
ATOM	363	CB	SER	A	159	3.627	33.414	19.111	1.00	37.04	6
ATOM	364	OG	SER	A	159	4.687	32.681	19.726	1.00	32.95	8
ATOM	365	C	SER	A	159	1.906	31.752	19.744	1.00	29.87	6
ATOM	366	O	SER	A	159	2.043	30.944	20.645	1.00	28.52	8
ATOM	367	N	SER	A	160	1.525	31.513	18.498	1.00	28.89	7
ATOM	368	CA	SER	A	160	1.020	30.167	18.155	1.00	31.12	6
ATOM	369	CB	SER	A	160	0.229	30.282	16.851	1.00	29.35	6
ATOM	370	OG	SER	A	160	0.979	30.793	15.778	1.00	39.68	8
ATOM	371	C	SER	A	160	2.125	29.135	18.122	1.00	31.20	6
ATOM	372	O	SER	A	160	1.852	27.946	18.180	1.00	40.09	8
ATOM	373	N	THR	A	161	3.379	29.492	17.936	1.00	29.17	7
ATOM	374	CA	THR	A	161	4.535	28.620	17.923	1.00	31.95	6
ATOM	375	CB	THR	A	161	5.728	29.296	17.195	1.00	32.45	6
ATOM	376	OG1	THR	A	161	5.881	30.601	17.775	1.00	30.29	8
ATOM	377	CG2	THR	A	161	5.551	29.428	15.705	1.00	29.68	6
ATOM	378	C	THR	A	161	4.993	28.340	19.364	1.00	29.18	6
ATOM	379	O	THR	A	161	5.917	27.498	19.536	1.00	30.20	8
ATOM	380	N	LEU	A	162	4.419	29.014	20.331	1.00	25.69	7
ATOM	381	CA	LEU	A	162	4.856	28.893	21.717	1.00	27.41	6
ATOM	382	CB	LEU	A	162	5.756	30.118	22.008	1.00	23.42	6
ATOM	383	CG	LEU	A	162	7.098	30.162	21.291	1.00	24.84	6
ATOM	384	CD1	LEU	A	162	7.779	31.516	21.585	1.00	23.56	6
ATOM	385	CD2	LEU	A	162	8.040	29.030	21.756	1.00	25.57	6
ATOM	386	C	LEU	A	162	3.724	28.789	22.704	1.00	27.32	6
ATOM	387	O	LEU	A	162	3.776	29.267	23.841	1.00	25.57	8
ATOM	388	N	THR	A	163	2.651	28.111	22.252	1.00	33.24	7
ATOM	389	CA	THR	A	163	1.435	27.945	23.005	1.00	34.43	6
ATOM	390	CB	THR	A	163	0.321	27.242	22.231	1.00	47.90	6
ATOM	391	OG1	THR	A	163	0.574	25.833	22.222	1.00	41.55	8
ATOM	392	CG2	THR	A	163	0.333	27.684	20.769	1.00	37.28	6
ATOM	393	C	THR	A	163	1.633	27.365	24.386	1.00	33.67	6
ATOM	394	O	THR	A	163	1.027	27.836	25.334	1.00	37.42	8
ATOM	395	N	ALA	A	164	2.588	26.420	24.481	1.00	34.03	7
ATOM	396	CA	ALA	A	164	2.861	25.891	25.801	1.00	33.86	6
ATOM	397	CB	ALA	A	164	3.368	24.474	25.747	1.00	38.55	6
ATOM	398	C	ALA	A	164	3.581	26.799	26.735	1.00	34.37	6
ATOM	399	O	ALA	A	164	3.702	26.455	27.918	1.00	32.28	8
ATOM	400	N	LEU	A	165	4.067	27.970	26.286	1.00	33.08	7
ATOM	401	CA	LEU	A	165	4.711	28.931	27.152	1.00	31.61	6
ATOM	402	CB	LEU	A	165	5.768	29.707	26.306	1.00	27.45	6
ATOM	403	CG	LEU	A	165	7.210	29.476	26.442	1.00	27.02	6
ATOM	404	CD1	LEU	A	165	8.028	30.517	25.763	1.00	24.12	6
ATOM	405	CD2	LEU	A	165	7.803	28.611	27.487	1.00	27.64	6
ATOM	406	C	LEU	A	165	3.814	30.032	27.651	1.00	29.91	6
ATOM	407	O	LEU	A	165	4.166	30.745	28.591	1.00	31.12	8
ATOM	408	N	THR	A	166	2.565	30.108	27.104	1.00	32.70	7
ATOM	409	CA	THR	A	166	1.679	31.174	27.587	1.00	39.86	6
ATOM	410	CB	THR	A	166	0.417	31.275	26.724	1.00	36.59	6
ATOM	411	OG1	THR	A	166	0.772	31.283	25.342	1.00	36.37	8
ATOM	412	CG2	THR	A	166	−0.426	32.496	27.035	1.00	43.25	6
ATOM	413	C	THR	A	166	1.507	31.273	29.078	1.00	40.96	6
ATOM	414	O	THR	A	166	1.550	32.372	29.663	1.00	38.71	8
ATOM	415	N	THR	A	167	1.389	30.162	29.818	1.00	41.60	7
ATOM	416	CA	THR	A	167	1.264	30.185	31.258	1.00	41.06	6
ATOM	417	CB	THR	A	167	1.145	28.770	31.877	1.00	56.92	6
ATOM	418	OG1	THR	A	167	0.505	27.882	30.956	1.00	64.37	8
ATOM	419	CG2	THR	A	167	0.315	28.860	33.144	1.00	53.26	6
ATOM	420	C	THR	A	167	2.386	30.920	31.965	1.00	38.21	6
ATOM	421	O	THR	A	167	2.297	31.748	32.872	1.00	38.00	8
ATOM	422	N	SER	A	168	3.588	30.592	31.464	1.00	36.02	7
ATOM	423	CA	SER	A	168	4.823	31.175	31.912	1.00	32.03	6
ATOM	424	CB	SER	A	168	5.950	30.393	31.219	1.00	39.61	6
ATOM	425	OG	SER	A	168	7.128	30.624	31.944	1.00	41.71	8
ATOM	426	C	SER	A	168	4.884	32.652	31.518	1.00	30.79	6
ATOM	427	O	SER	A	168	5.266	33.502	32.301	1.00	33.91	8
ATOM	428	N	VAL	A	169	4.426	32.962	30.314	1.00	35.38	7
ATOM	429	CA	VAL	A	169	4.455	34.357	29.876	1.00	27.71	6
ATOM	430	CB	VAL	A	169	4.121	34.448	28.385	1.00	29.96	6
ATOM	431	CG1	VAL	A	169	4.086	35.924	27.943	1.00	25.54	6
ATOM	432	CG2	VAL	A	169	5.195	33.724	27.582	1.00	33.79	6
ATOM	433	C	VAL	A	169	3.604	35.213	30.817	1.00	32.85	6
ATOM	434	O	VAL	A	169	3.951	36.282	31.333	1.00	35.86	8
ATOM	435	N	LEU	A	170	2.431	34.704	31.152	1.00	35.39	7
ATOM	436	CA	LEU	A	170	1.500	35.385	32.050	1.00	39.23	6
ATOM	437	CB	LEU	A	170	0.244	34.542	32.100	1.00	35.15	6
ATOM	438	CG	LEU	A	170	−0.801	34.822	31.014	1.00	38.80	6
ATOM	439	CD1	LEU	A	170	−2.126	34.272	31.565	1.00	42.41	6
ATOM	440	CD2	LEU	A	170	−0.976	36.292	30.731	1.00	45.02	6
ATOM	441	C	LEU	A	170	2.081	35.543	33.439	1.00	37.13	6
ATOM	442	O	LEU	A	170	2.037	36.613	34.032	1.00	38.03	8
ATOM	443	N	LYS	A	171	2.655	34.441	33.932	1.00	39.80	7
ATOM	444	CA	LYS	A	171	3.240	34.460	35.275	1.00	44.19	6
ATOM	445	CB	LYS	A	171	3.846	33.078	35.586	1.00	61.33	6
ATOM	446	CG	LYS	A	171	4.568	33.045	36.927	1.00	70.55	6
ATOM	447	CD	LYS	A	171	3.614	33.375	38.065	1.00	82.76	6
ATOM	448	CE	LYS	A	171	4.325	33.536	39.396	1.00	86.15	6
ATOM	449	NZ	LYS	A	171	3.605	34.470	40.306	1.00	86.50	7
ATOM	450	C	LYS	A	171	4.330	35.495	35.417	1.00	42.25	6
ATOM	451	O	LYS	A	171	4.501	36.069	36.505	1.00	40.60	8
ATOM	452	N	ASN	A	172	5.098	35.697	34.326	1.00	34.05	7
ATOM	453	CA	ASN	A	172	6.151	36.713	34.380	1.00	32.66	6
ATOM	454	CB	ASN	A	172	7.200	36.380	33.287	1.00	39.13	6
ATOM	455	CG	ASN	A	172	8.163	35.288	33.667	1.00	44.80	6
ATOM	456	OD1	ASN	A	172	9.197	35.585	34.263	1.00	49.14	8
ATOM	457	ND2	ASN	A	172	7.897	34.039	33.329	1.00	37.24	7
ATOM	458	C	ASN	A	172	5.661	38.135	34.153	1.00	32.11	6
ATOM	459	O	ASN	A	172	6.468	39.055	33.977	1.00	34.88	8
ATOM	460	N	ASN	A	173	4.358	38.394	34.203	1.00	31.68	7
ATOM	461	CA	ASN	A	173	3.768	39.716	34.061	1.00	29.24	6
ATOM	462	CB	ASN	A	173	4.009	40.629	35.235	1.00	35.84	6
ATOM	463	CG	ASN	A	173	3.450	39.955	36.506	1.00	36.42	6
ATOM	464	OD1	ASN	A	173	2.591	39.085	36.396	1.00	39.55	8
ATOM	465	ND2	ASN	A	173	4.002	40.381	37.626	1.00	53.62	7
ATOM	466	C	ASN	A	173	4.197	40.404	32.740	1.00	29.47	6
ATOM	467	O	ASN	A	173	4.307	41.640	32.703	1.00	32.55	8
ATOM	468	N	LEU	A	174	4.282	39.567	31.697	1.00	31.56	7
ATOM	469	CA	LEU	A	174	4.668	40.131	30.389	1.00	27.42	6
ATOM	470	CB	LEU	A	174	5.487	39.094	29.567	1.00	27.30	6
ATOM	471	CG	LEU	A	174	6.789	38.694	30.298	1.00	29.12	6
ATOM	472	CD1	LEU	A	174	7.411	37.496	29.567	1.00	28.87	6
ATOM	473	CD2	LEU	A	174	7.755	39.890	30.307	1.00	30.51	6
ATOM	474	C	LEU	A	174	3.472	40.556	29.553	1.00	30.31	6
ATOM	475	O	LEU	A	174	3.738	41.133	28.468	1.00	26.30	8
ATOM	476	N	CYS	A	175	2.255	40.276	30.006	1.00	30.27	7
ATOM	477	CA	CYS	A	175	1.110	40.728	29.213	1.00	30.49	6
ATOM	478	C	CYS	A	175	0.364	41.868	29.883	1.00	30.71	6
ATOM	479	O	CYS	A	175	0.383	41.960	31.119	1.00	28.85	8
ATOM	480	CB	CYS	A	175	0.225	39.531	28.885	1.00	33.22	6
ATOM	481	SG	CYS	A	175	1.157	38.382	27.797	1.00	34.32	16
ATOM	482	N	PRO	A	176	−0.216	42.747	29.126	1.00	27.02	7
ATOM	483	CD	PRO	A	176	−0.202	42.778	27.620	1.00	27.31	6
ATOM	484	CA	PRO	A	176	−1.031	43.860	29.607	1.00	29.02	6
ATOM	485	CB	PRO	A	176	−1.802	44.330	28.356	1.00	30.75	6
ATOM	486	CG	PRO	A	176	−0.681	44.201	27.369	1.00	29.79	6
ATOM	487	C	PRO	A	176	−2.061	43.417	30.656	1.00	28.74	6
ATOM	488	O	PRO	A	176	−2.600	42.326	30.586	1.00	29.00	8
ATOM	489	N	SER	A	177	−2.232	44.390	31.582	1.00	30.95	7
ATOM	490	CA	SER	A	177	−3.173	44.142	32.688	1.00	35.36	6
ATOM	491	CB	SER	A	177	−3.415	45.461	33.435	1.00	36.82	6
ATOM	492	OG	SER	A	177	−2.202	46.102	33.764	1.00	45.84	8
ATOM	493	C	SER	A	177	−4.485	43.656	32.120	1.00	38.68	6
ATOM	494	O	SER	A	177	−4.918	44.231	31.107	1.00	42.81	8
ATOM	495	N	GLY	A	178	−5.101	42.644	32.713	1.00	42.54	7
ATOM	496	CA	GLY	A	178	−6.357	42.145	32.183	1.00	44.10	6
ATOM	497	C	GLY	A	178	−6.180	40.771	31.571	1.00	47.58	6
ATOM	498	O	GLY	A	178	−7.075	39.934	31.641	1.00	48.95	8
ATOM	499	N	SER	A	179	−5.012	40.548	30.951	1.00	42.04	7
ATOM	500	CA	SER	A	179	−4.715	39.262	30.363	1.00	39.16	6
ATOM	501	CB	SER	A	179	−3.278	39.360	29.771	1.00	35.52	6
ATOM	502	OG	SER	A	179	−3.444	40.056	28.515	1.00	44.97	8
ATOM	503	C	SER	A	179	−4.702	38.152	31.410	1.00	41.15	6
ATOM	504	O	SER	A	179	−4.185	38.285	32.522	1.00	38.03	8
ATOM	505	N	ASN	A	180	−5.273	37.027	31.030	1.00	37.43	7
ATOM	506	CA	ASN	A	180	−5.370	35.833	31.843	1.00	38.91	6
ATOM	507	CB	ASN	A	180	−6.498	35.968	32.868	1.00	43.64	6
ATOM	508	CG	ASN	A	180	−7.760	36.496	32.206	1.00	50.72	6
ATOM	509	OD1	ASN	A	180	−7.969	37.713	32.184	1.00	47.95	8
ATOM	510	ND2	ASN	A	180	−8.569	35.607	31.652	1.00	40.10	7
ATOM	511	C	ASN	A	180	−5.659	34.707	30.844	1.00	39.79	6
ATOM	512	O	ASN	A	180	−5.906	35.014	29.664	1.00	41.96	8
ATOM	513	N	ILE	A	181	−5.508	33.473	31.256	1.00	40.01	7
ATOM	514	CA	ILE	A	181	−5.631	32.321	30.375	1.00	35.08	6
ATOM	515	CB	ILE	A	181	−5.369	31.007	31.114	1.00	43.35	6
ATOM	516	CG2	ILE	A	181	−6.180	30.867	32.394	1.00	50.56	6
ATOM	517	CG1	ILE	A	181	−5.664	29.800	30.226	1.00	37.17	6
ATOM	518	CD1	ILE	A	181	−5.177	28.476	30.772	1.00	61.09	6
ATOM	519	C	ILE	A	181	−6.930	32.343	29.593	1.00	38.56	6
ATOM	520	O	ILE	A	181	−6.896	32.286	28.357	1.00	39.50	8
ATOM	521	N	ILE	A	182	−8.065	32.520	30.276	1.00	31.14	7
ATOM	522	CA	ILE	A	182	−9.323	32.541	29.548	1.00	33.99	6
ATOM	523	CB	ILE	A	182	−10.590	32.395	30.398	1.00	35.20	6
ATOM	524	CG2	ILE	A	182	−11.798	32.450	29.440	1.00	38.49	6
ATOM	525	CG1	ILE	A	182	−10.615	30.996	31.030	1.00	33.92	6
ATOM	526	CD1	ILE	A	182	−11.972	30.794	31.679	1.00	41.51	6
ATOM	527	C	ILE	A	182	−9.453	33.664	28.548	1.00	33.21	6
ATOM	528	O	ILE	A	182	−9.686	33.395	27.358	1.00	32.00	8
ATOM	529	N	SER	A	183	−9.300	34.909	28.992	1.00	32.06	7
ATOM	530	CA	SER	A	183	−9.481	36.019	28.046	1.00	30.17	6
ATOM	531	CB	SER	A	183	−9.173	37.363	28.705	1.00	40.84	6
ATOM	532	OG	SER	A	183	−7.832	37.387	29.180	1.00	50.43	8
ATOM	533	C	SER	A	183	−8.539	35.849	26.867	1.00	29.79	6
ATOM	534	O	SER	A	183	−8.841	36.209	25.719	1.00	30.43	8
ATOM	535	N	ASN	A	184	−7.325	35.342	27.158	1.00	29.85	7
ATOM	536	CA	ASN	A	184	−6.366	35.206	26.073	1.00	29.42	6
ATOM	537	CB	ASN	A	184	−4.954	35.100	26.613	1.00	32.69	6
ATOM	538	CG	ASN	A	184	−3.909	35.579	25.617	1.00	39.32	6
ATOM	539	OD1	ASN	A	184	−3.902	36.737	25.180	1.00	38.73	8
ATOM	540	ND2	ASN	A	184	−3.026	34.659	25.253	1.00	37.01	7
ATOM	541	C	ASN	A	184	−6.767	34.168	25.046	1.00	29.90	6
ATOM	542	O	ASN	A	184	−6.416	34.312	23.886	1.00	30.55	8
ATOM	543	N	LEU	A	185	−7.594	33.180	25.400	1.00	28.17	7
ATOM	544	CA	LEU	A	185	−8.022	32.190	24.418	1.00	28.14	6
ATOM	545	CB	LEU	A	185	−8.792	31.069	25.170	1.00	31.80	6
ATOM	546	CG	LEU	A	185	−7.873	30.228	26.077	1.00	37.24	6
ATOM	547	CD1	LEU	A	185	−8.734	29.247	26.874	1.00	38.22	6
ATOM	548	CD2	LEU	A	185	−6.862	29.482	25.200	1.00	30.41	6
ATOM	549	C	LEU	A	185	−8.978	32.794	23.390	1.00	25.61	6
ATOM	550	O	LEU	A	185	−9.127	32.198	22.304	1.00	29.28	8
ATOM	551	N	PHE	A	186	−9.577	33.930	23.688	1.00	25.10	7
ATOM	552	CA	PHE	A	186	−10.524	34.523	22.720	1.00	28.91	6
ATOM	553	CB	PHE	A	186	−11.725	35.124	23.488	1.00	28.71	6
ATOM	554	CG	PHE	A	186	−12.636	34.083	24.083	1.00	31.64	6
ATOM	555	CD1	PHE	A	186	−12.428	33.583	25.332	1.00	30.09	6
ATOM	556	CD2	PHE	A	186	−13.724	33.670	23.346	1.00	29.23	6
ATOM	557	CE1	PHE	A	186	−13.280	32.604	25.875	1.00	34.13	6
ATOM	558	CE2	PHE	A	186	−14.599	32.724	23.893	1.00	27.11	6
ATOM	559	CZ	PHE	A	186	−14.364	32.192	25.124	1.00	31.22	6
ATOM	560	C	PHE	A	186	−9.888	35.661	21.919	1.00	28.36	6
ATOM	561	O	PHE	A	186	−10.575	36.472	21.302	1.00	30.96	8
ATOM	562	N	LYS	A	187	−8.558	35.744	21.959	1.00	29.55	7
ATOM	563	CA	LYS	A	187	−7.849	36.800	21.204	1.00	30.12	6
ATOM	564	CB	LYS	A	187	−6.981	37.575	22.229	1.00	30.88	6
ATOM	565	CG	LYS	A	187	−7.821	38.654	22.890	1.00	43.39	6
ATOM	566	CD	LYS	A	187	−7.047	39.391	23.958	1.00	48.15	6
ATOM	567	CE	LYS	A	187	−6.085	40.405	23.339	1.00	41.67	6
ATOM	568	NZ	LYS	A	187	−5.759	41.430	24.369	1.00	42.64	7
ATOM	569	C	LYS	A	187	−6.869	36.185	20.213	1.00	27.72	6
ATOM	570	O	LYS	A	187	−6.370	35.086	20.445	1.00	28.84	8
ATOM	571	N	GLU	A	188	−6.606	36.916	19.110	1.00	26.40	7
ATOM	572	CA	GLU	A	188	−5.608	36.498	18.144	1.00	24.95	6
ATOM	573	CB	GLU	A	188	−5.558	37.520	16.994	1.00	30.53	6
ATOM	574	CG	GLU	A	188	−6.924	37.605	16.315	1.00	39.56	6
ATOM	575	CD	GLU	A	188	−6.932	38.457	15.068	1.00	58.60	6
ATOM	576	OE1	GLU	A	188	−6.597	39.661	15.133	1.00	57.62	8
ATOM	577	OE2	GLU	A	188	−7.290	37.897	14.009	1.00	64.79	8
ATOM	578	C	GLU	A	188	−4.194	36.601	18.808	1.00	20.96	6
ATOM	579	O	GLU	A	188	−4.014	37.439	19.683	1.00	25.27	8
ATOM	580	N	ASP	A	189	−3.380	35.673	18.394	1.00	25.32	7
ATOM	581	CA	ASP	A	189	−2.027	35.623	18.967	1.00	22.63	6
ATOM	582	CB	ASP	A	189	−1.380	34.237	18.781	1.00	28.31	6
ATOM	583	CG	ASP	A	189	−0.770	34.114	17.422	1.00	24.61	6
ATOM	584	OD1	ASP	A	189	0.473	33.884	17.302	1.00	27.48	8
ATOM	585	OD2	ASP	A	189	−1.347	34.337	16.351	1.00	35.01	8
ATOM	586	C	ASP	A	189	−1.167	36.691	18.300	1.00	22.86	6
ATOM	587	O	ASP	A	189	−1.537	37.330	17.273	1.00	24.00	8
ATOM	588	N	CYS	A	190	0.065	36.811	18.805	1.00	22.75	7
ATOM	589	CA	CYS	A	190	0.956	37.851	18.216	1.00	21.64	6
ATOM	590	C	CYS	A	190	1.352	37.562	16.782	1.00	21.74	6
ATOM	591	O	CYS	A	190	1.569	38.596	16.081	1.00	24.29	8
ATOM	592	CB	CYS	A	190	2.133	38.128	19.101	1.00	23.60	6
ATOM	593	SG	CYS	A	190	1.730	38.711	20.756	1.00	26.96	16
ATOM	594	N	HIS	A	191	1.496	36.339	16.299	1.00	22.50	7
ATOM	595	CA	HIS	A	191	1.881	36.196	14.901	1.00	21.71	6
ATOM	596	CB	HIS	A	191	2.232	34.740	14.596	1.00	26.64	6
ATOM	597	CG	HIS	A	191	3.551	34.362	15.222	1.00	26.82	6
ATOM	598	CD2	HIS	A	191	4.355	34.965	16.093	1.00	26.94	6
ATOM	599	ND1	HIS	A	191	4.129	33.171	14.866	1.00	29.12	7
ATOM	600	CE1	HIS	A	191	5.285	33.094	15.532	1.00	25.60	6
ATOM	601	NE2	HIS	A	191	5.427	34.114	16.334	1.00	25.91	7
ATOM	602	C	HIS	A	191	0.831	36.773	14.002	1.00	21.74	6
ATOM	603	O	HIS	A	191	1.141	37.315	12.904	1.00	24.92	8
ATOM	604	N	GLN	A	192	−0.436	36.475	14.363	1.00	26.00	7
ATOM	605	CA	GLN	A	192	−1.530	36.988	13.529	1.00	26.00	6
ATOM	606	CB	GLN	A	192	−2.890	36.549	14.130	1.00	25.26	6
ATOM	607	CG	GLN	A	192	−3.979	37.056	13.177	1.00	36.23	6
ATOM	608	CD	GLN	A	192	−3.954	36.524	11.775	1.00	42.56	6
ATOM	609	OE1	GLN	A	192	−4.126	35.350	11.486	1.00	46.38	8
ATOM	610	NE2	GLN	A	192	−3.772	37.366	10.753	1.00	34.35	7
ATOM	611	C	GLN	A	192	−1.505	38.503	13.534	1.00	25.56	6
ATOM	612	O	GLN	A	192	−1.717	39.139	12.485	1.00	25.01	8
ATOM	613	N	LYS	A	193	−1.318	39.155	14.685	1.00	22.99	7
ATOM	614	CA	LYS	A	193	−1.206	40.597	14.767	1.00	21.22	6
ATOM	615	CB	LYS	A	193	−1.188	41.124	16.218	1.00	20.84	6
ATOM	616	CG	LYS	A	193	−2.495	40.778	16.896	1.00	22.00	6
ATOM	617	CD	LYS	A	193	−3.688	41.482	16.250	1.00	28.69	6
ATOM	618	CE	LYS	A	193	−4.963	41.573	17.081	1.00	42.13	6
ATOM	619	NZ	LYS	A	193	−4.903	42.588	18.149	1.00	42.68	7
ATOM	620	C	LYS	A	193	−0.033	41.140	13.970	1.00	23.50	6
ATOM	621	O	LYS	A	193	−0.182	42.216	13.366	1.00	24.64	8
ATOM	622	N	ILE	A	194	1.095	40.444	13.924	1.00	20.30	7
ATOM	623	CA	ILE	A	194	2.211	40.878	13.074	1.00	22.70	6
ATOM	624	CB	ILE	A	194	3.436	39.972	13.318	1.00	22.09	6
ATOM	625	CG2	ILE	A	194	4.487	40.101	12.184	1.00	23.81	6
ATOM	626	CG1	ILE	A	194	3.920	40.404	14.714	1.00	20.79	6
ATOM	627	CD1	ILE	A	194	4.915	39.428	15.349	1.00	24.12	6
ATOM	628	C	ILE	A	194	1.767	40.836	11.632	1.00	22.66	6
ATOM	629	O	ILE	A	194	1.942	41.791	10.879	1.00	23.54	8
ATOM	630	N	ASP	A	195	1.079	39.728	11.287	1.00	25.86	7
ATOM	631	CA	ASP	A	195	0.636	39.644	9.875	1.00	28.42	6
ATOM	632	CB	ASP	A	195	−0.154	38.334	9.694	1.00	30.81	6
ATOM	633	CG	ASP	A	195	0.736	37.219	9.172	1.00	43.61	6
ATOM	634	OD1	ASP	A	195	0.354	36.035	9.317	1.00	40.90	8
ATOM	635	OD2	ASP	A	195	1.786	37.567	8.637	1.00	40.27	8
ATOM	636	C	ASP	A	195	−0.330	40.800	9.581	1.00	25.57	6
ATOM	637	O	ASP	A	195	−0.257	41.436	8.510	1.00	28.18	8
ATOM	638	N	ASP	A	196	−1.223	41.116	10.487	1.00	25.86	7
ATOM	639	CA	ASP	A	196	−2.214	42.186	10.297	1.00	27.70	6
ATOM	640	CB	ASP	A	196	−3.190	42.304	11.477	1.00	27.67	6
ATOM	641	CG	ASP	A	196	−4.130	41.117	11.536	1.00	35.55	6
ATOM	642	OD1	ASP	A	196	−4.182	40.386	10.527	1.00	37.44	8
ATOM	643	OD2	ASP	A	196	−4.830	40.899	12.549	1.00	40.00	8
ATOM	644	C	ASP	A	196	−1.520	43.522	10.070	1.00	30.21	6
ATOM	645	O	ASP	A	196	−1.970	44.383	9.300	1.00	29.23	8
ATOM	646	N	LEU	A	197	−0.448	43.765	10.821	1.00	26.41	7
ATOM	647	CA	LEU	A	197	0.329	44.989	10.638	1.00	24.54	6
ATOM	648	CB	LEU	A	197	1.464	45.064	11.623	1.00	22.89	6
ATOM	649	CG	LEU	A	197	2.400	46.254	11.546	1.00	24.59	6
ATOM	650	CD1	LEU	A	197	1.789	47.610	11.857	1.00	28.10	6
ATOM	651	CD2	LEU	A	197	3.592	45.960	12.455	1.00	27.91	6
ATOM	652	C	LEU	A	197	0.858	45.132	9.195	1.00	22.96	6
ATOM	653	O	LEU	A	197	0.744	46.208	8.599	1.00	25.34	8
ATOM	654	N	PHE	A	198	1.456	44.113	8.670	1.00	22.19	7
ATOM	655	CA	PHE	A	198	2.074	44.173	7.320	1.00	26.14	6
ATOM	656	CB	PHE	A	198	3.191	43.158	7.237	1.00	25.23	6
ATOM	657	CG	PHE	A	198	4.401	43.555	8.043	1.00	24.37	6
ATOM	658	CD1	PHE	A	198	4.583	43.021	9.311	1.00	27.98	6
ATOM	659	CD2	PHE	A	198	5.290	44.493	7.600	1.00	26.06	6
ATOM	660	CE1	PHE	A	198	5.669	43.416	10.068	1.00	26.50	6
ATOM	661	CE2	PHE	A	198	6.376	44.898	8.324	1.00	26.50	6
ATOM	662	CZ	PHE	A	198	6.583	44.349	9.584	1.00	24.03	6
ATOM	663	C	PHE	A	198	1.063	44.075	6.215	1.00	27.88	6
ATOM	664	O	PHE	A	198	1.389	44.527	5.119	1.00	29.23	8
ATOM	665	N	SER	A	199	−0.163	43.662	6.554	1.00	30.11	7
ATOM	666	CA	SER	A	199	−1.196	43.609	5.519	1.00	32.39	6
ATOM	667	CB	SER	A	199	−1.975	42.287	5.669	1.00	34.42	6
ATOM	668	OG	SER	A	199	−2.802	42.466	6.800	1.00	43.38	8
ATOM	669	C	SER	A	199	−2.129	44.790	5.572	1.00	32.01	6
ATOM	670	O	SER	A	199	−3.108	44.873	4.809	1.00	36.63	8
ATOM	671	N	GLY	A	200	−1.936	45.715	6.497	1.00	26.46	7
ATOM	672	CA	GLY	A	200	−2.719	46.913	6.622	1.00	30.24	6
ATOM	673	C	GLY	A	200	−4.089	46.697	7.221	1.00	37.40	6
ATOM	674	O	GLY	A	200	−5.045	47.396	6.885	1.00	42.48	8
ATOM	675	N	LYS	A	201	−4.195	45.797	8.186	1.00	35.07	7
ATOM	676	CA	LYS	A	201	−5.466	45.583	8.887	1.00	39.63	6
ATOM	677	CB	LYS	A	201	−5.761	44.094	9.088	1.00	41.19	6
ATOM	678	CG	LYS	A	201	−5.538	43.369	7.769	1.00	43.81	6
ATOM	679	CD	LYS	A	201	−6.418	42.142	7.586	1.00	52.66	6
ATOM	680	CE	LYS	A	201	−6.541	41.945	6.069	1.00	53.36	6
ATOM	681	NZ	LYS	A	201	−6.396	43.284	5.415	1.00	53.44	7
ATOM	682	C	LYS	A	201	−5.373	46.308	10.219	1.00	44.11	6
ATOM	683	O	LYS	A	201	−5.967	47.376	10.421	1.00	48.21	8
ATOM	684	N	HIS	A	202	−4.645	45.700	11.127	1.00	41.73	7
ATOM	685	CA	HIS	A	202	−4.429	46.288	12.448	1.00	47.06	6
ATOM	686	C	HIS	A	202	−4.966	47.699	12.541	1.00	50.86	6
ATOM	687	O	HIS	A	202	−6.043	47.930	13.140	1.00	51.62	8
ATOM	688	CB	HIS	A	202	−2.892	46.295	12.678	1.00	39.32	6
ATOM	689	CG	HIS	A	202	−2.571	45.523	13.918	1.00	54.43	6
ATOM	690	ND1	HIS	A	202	−3.177	45.808	15.124	1.00	60.36	7
ATOM	691	CD2	HIS	A	202	−1.740	44.481	14.121	1.00	32.15	6
ATOM	692	CE1	HIS	A	202	−2.714	44.975	16.050	1.00	58.04	6
ATOM	693	NE2	HIS	A	202	−1.847	44.161	15.461	1.00	66.87	7
ATOM	694	CB	PHE	B	213	19.717	35.136	16.091	0.00	34.83	6
ATOM	695	CG	PHE	B	213	20.197	34.465	17.321	0.00	44.80	6
ATOM	696	CD1	PHE	B	213	21.533	34.182	17.521	0.00	58.13	6
ATOM	697	CD2	PHE	B	213	19.319	34.146	18.350	0.00	62.44	6
ATOM	698	CE1	PHE	B	213	21.983	33.580	18.677	0.00	56.87	6
ATOM	699	CE2	PHE	B	213	19.751	33.535	19.518	0.00	69.83	6
ATOM	700	CZ	PHE	B	213	21.091	33.243	19.683	0.00	53.63	6
ATOM	701	C	PHE	B	213	18.658	35.823	13.931	1.00	38.28	6
ATOM	702	O	PHE	B	213	19.511	36.353	13.199	1.00	40.98	8
ATOM	703	N	PHE	B	213	20.058	33.920	13.960	0.00	39.06	7
ATOM	704	CA	PHE	B	213	18.949	34.523	14.688	1.00	37.25	6
ATOM	705	N	VAL	B	214	17.444	36.311	14.059	1.00	28.83	7
ATOM	706	CA	VAL	B	214	17.111	37.604	13.427	1.00	27.89	6
ATOM	707	CB	VAL	B	214	15.585	37.806	13.482	1.00	22.89	6
ATOM	708	CG1	VAL	B	214	15.193	39.183	12.890	1.00	26.71	6
ATOM	709	CG2	VAL	B	214	14.947	36.736	12.598	1.00	28.90	6
ATOM	710	C	VAL	B	214	17.745	38.665	14.270	1.00	28.77	6
ATOM	711	O	VAL	B	214	17.533	38.794	15.474	1.00	28.76	8
ATOM	712	N	ASN	B	215	18.444	39.614	13.620	1.00	29.41	7
ATOM	713	CA	ASN	B	215	19.127	40.646	14.396	1.00	28.39	6
ATOM	714	CB	ASN	B	215	20.442	40.928	13.643	1.00	32.91	6
ATOM	715	CG	ASN	B	215	21.148	42.093	14.265	1.00	39.44	6
ATOM	716	OD1	ASN	B	215	21.865	41.881	15.245	1.00	53.33	8
ATOM	717	ND2	ASN	B	215	20.905	43.288	13.757	1.00	37.32	7
ATOM	718	C	ASN	B	215	18.259	41.895	14.501	1.00	27.27	6
ATOM	719	O	ASN	B	215	17.705	42.313	13.486	1.00	27.80	8
ATOM	720	N	LYS	B	216	18.223	42.525	15.657	1.00	29.93	7
ATOM	721	CA	LYS	B	216	17.420	43.699	15.889	1.00	30.04	6
ATOM	722	CB	LYS	B	216	17.601	44.227	17.320	1.00	38.33	6
ATOM	723	CG	LYS	B	216	17.259	45.678	17.506	1.00	51.27	6
ATOM	724	CD	LYS	B	216	18.220	46.399	18.436	1.00	60.50	6
ATOM	725	CE	LYS	B	216	17.949	47.901	18.401	1.00	41.22	6
ATOM	726	NZ	LYS	B	216	18.269	48.521	19.723	1.00	56.24	7
ATOM	727	C	LYS	B	216	17.571	44.843	14.896	1.00	32.97	6
ATOM	728	O	LYS	B	216	16.642	45.376	14.285	1.00	32.82	8
ATOM	729	N	ASP	B	217	18.815	45.234	14.662	1.00	30.39	7
ATOM	730	CA	ASP	B	217	19.079	46.384	13.755	1.00	28.18	6
ATOM	731	CB	ASP	B	217	20.615	46.597	13.856	1.00	37.07	6
ATOM	732	CG	ASP	B	217	20.974	47.025	15.271	1.00	50.77	6
ATOM	733	OD1	ASP	B	217	20.325	47.961	15.789	1.00	50.99	8
ATOM	734	OD2	ASP	B	217	21.873	46.381	15.855	1.00	48.20	8
ATOM	735	C	ASP	B	217	18.710	46.045	12.326	1.00	27.65	6
ATOM	736	O	ASP	B	217	18.209	46.917	11.586	1.00	29.68	8
ATOM	737	N	GLN	B	218	18.945	44.818	11.903	1.00	26.96	7
ATOM	738	CA	GLN	B	218	18.641	44.363	10.567	1.00	26.89	6
ATOM	739	CB	GLN	B	218	19.194	43.015	10.137	1.00	28.58	6
ATOM	740	CG	GLN	B	218	18.876	42.625	8.703	1.00	28.47	6
ATOM	741	CD	GLN	B	218	19.550	43.604	7.748	1.00	39.80	6
ATOM	742	OE1	GLN	B	218	20.732	43.897	7.957	1.00	49.83	8
ATOM	743	NE2	GLN	B	218	18.880	44.111	6.730	1.00	37.47	7
ATOM	744	C	GLN	B	218	17.118	44.408	10.342	1.00	26.99	6
ATOM	745	O	GLN	B	218	16.688	44.970	9.349	1.00	23.66	8
ATOM	746	N	ILE	B	219	16.361	43.806	11.268	1.00	22.98	7
ATOM	747	CA	ILE	B	219	14.909	43.777	11.054	1.00	22.46	6
ATOM	748	CB	ILE	B	219	14.209	42.791	11.998	1.00	24.01	6
ATOM	749	CG2	ILE	B	219	14.320	43.076	13.484	1.00	23.36	6
ATOM	750	CG1	ILE	B	219	12.723	42.606	11.625	1.00	27.82	6
ATOM	751	CD1	ILE	B	219	12.575	42.170	10.187	1.00	28.39	6
ATOM	752	C	ILE	B	219	14.345	45.182	11.118	1.00	23.15	6
ATOM	753	O	ILE	B	219	13.418	45.528	10.374	1.00	24.69	8
ATOM	754	N	ALA	B	220	14.870	46.029	11.972	1.00	21.24	7
ATOM	755	CA	ALA	B	220	14.395	47.403	12.053	1.00	23.02	6
ATOM	756	CB	ALA	B	220	14.940	48.146	13.226	1.00	28.82	6
ATOM	757	C	ALA	B	220	14.573	48.131	10.730	1.00	23.96	6
ATOM	758	O	ALA	B	220	13.704	48.838	10.261	1.00	23.87	8
ATOM	759	N	LYS	B	221	15.767	47.916	10.161	1.00	25.79	7
ATOM	760	CA	LYS	B	221	16.086	48.555	8.865	1.00	26.23	6
ATOM	761	CB	LYS	B	221	17.518	48.106	8.505	1.00	23.73	6
ATOM	762	CG	LYS	B	221	17.859	48.602	7.084	1.00	32.18	6
ATOM	763	CD	LYS	B	221	19.349	48.458	6.835	1.00	48.70	6
ATOM	764	CE	LYS	B	221	19.738	48.828	5.402	1.00	49.31	6
ATOM	765	NZ	LYS	B	221	18.639	48.516	4.446	1.00	60.95	7
ATOM	766	C	LYS	B	221	15.111	48.086	7.783	1.00	26.25	6
ATOM	767	O	LYS	B	221	14.595	48.870	6.961	1.00	24.99	8
ATOM	768	N	ASP	B	222	14.904	46.759	7.727	1.00	24.13	7
ATOM	769	CA	ASP	B	222	13.988	46.167	6.775	1.00	23.28	6
ATOM	770	CB	ASP	B	222	13.982	44.670	6.968	1.00	26.58	6
ATOM	771	CG	ASP	B	222	15.288	43.945	6.671	1.00	37.75	6
ATOM	772	OD1	ASP	B	222	16.177	44.545	6.002	1.00	35.10	8
ATOM	773	OD2	ASP	B	222	15.441	42.777	7.110	1.00	31.39	8
ATOM	774	C	ASP	B	222	12.586	46.747	6.890	1.00	24.42	6
ATOM	775	O	ASP	B	222	11.842	46.970	5.918	1.00	25.24	8
ATOM	776	N	VAL	B	223	12.130	46.917	8.182	1.00	22.06	7
ATOM	777	CA	VAL	B	223	10.773	47.427	8.389	1.00	20.51	6
ATOM	778	CB	VAL	B	223	10.346	47.208	9.897	1.00	19.83	6
ATOM	779	CG1	VAL	B	223	8.934	47.819	10.090	1.00	20.77	6
ATOM	780	CG2	VAL	B	223	10.265	45.693	10.021	1.00	22.25	6
ATOM	781	C	VAL	B	223	10.653	48.898	8.031	1.00	21.93	6
ATOM	782	O	VAL	B	223	9.636	49.304	7.482	1.00	23.92	8
ATOM	783	N	LYS	B	224	11.687	49.704	8.307	1.00	24.30	7
ATOM	784	CA	LYS	B	224	11.651	51.102	7.873	1.00	22.31	6
ATOM	785	CB	LYS	B	224	12.864	51.841	8.430	1.00	23.89	6
ATOM	786	CG	LYS	B	224	12.817	51.931	9.959	1.00	26.32	6
ATOM	787	CD	LYS	B	224	14.034	52.827	10.307	1.00	30.62	6
ATOM	788	CE	LYS	B	224	14.495	52.556	11.713	1.00	36.62	6
ATOM	789	NZ	LYS	B	224	15.946	52.883	11.937	1.00	36.97	7
ATOM	790	C	LYS	B	224	11.724	51.116	6.341	1.00	22.74	6
ATOM	791	O	LYS	B	224	11.013	51.991	5.787	1.00	24.89	8
ATOM	792	N	GLN	B	225	12.380	50.174	5.720	1.00	23.32	7
ATOM	793	CA	GLN	B	225	12.371	50.203	4.236	1.00	25.62	6
ATOM	794	CB	GLN	B	225	13.406	49.210	3.710	1.00	32.12	6
ATOM	795	CG	GLN	B	225	13.606	49.177	2.203	1.00	38.34	6
ATOM	796	CD	GLN	B	225	14.606	48.107	1.788	1.00	49.03	6
ATOM	797	OE1	GLN	B	225	14.901	47.117	2.477	1.00	39.12	8
ATOM	798	NE2	GLN	B	225	15.160	48.322	0.591	1.00	50.68	7
ATOM	799	C	GLN	B	225	11.015	49.920	3.658	1.00	26.59	6
ATOM	800	O	GLN	B	225	10.508	50.492	2.680	1.00	27.36	8
ATOM	801	N	PHE	B	226	10.302	48.952	4.258	1.00	25.80	7
ATOM	802	CA	PHE	B	226	8.971	48.534	3.933	1.00	20.22	6
ATOM	803	CB	PHE	B	226	8.522	47.339	4.808	1.00	24.02	6
ATOM	804	CG	PHE	B	226	7.074	47.012	4.701	1.00	23.15	6
ATOM	805	CD1	PHE	B	226	6.628	46.093	3.758	1.00	31.92	6
ATOM	806	CD2	PHE	B	226	6.116	47.603	5.521	1.00	24.40	6
ATOM	807	CE1	PHE	B	226	5.300	45.763	3.633	1.00	31.15	6
ATOM	808	CE2	PHE	B	226	4.777	47.282	5.405	1.00	27.17	6
ATOM	809	CZ	PHE	B	226	4.258	46.347	4.480	1.00	30.58	6
ATOM	810	C	PHE	B	226	8.048	49.722	4.129	1.00	25.25	6
ATOM	811	O	PHE	B	226	7.144	49.992	3.322	1.00	24.87	8
ATOM	812	N	TYR	B	227	8.134	50.368	5.323	1.00	23.99	7
ATOM	813	CA	TYR	B	227	7.292	51.560	5.541	1.00	22.94	6
ATOM	814	CB	TYR	B	227	7.513	52.055	6.995	1.00	24.23	6
ATOM	815	CG	TYR	B	227	6.875	53.415	7.212	1.00	23.07	6
ATOM	816	CD1	TYR	B	227	5.501	53.551	7.469	1.00	22.96	6
ATOM	817	CE1	TYR	B	227	4.873	54.758	7.629	1.00	22.01	6
ATOM	818	CD2	TYR	B	227	7.591	54.580	7.177	1.00	23.12	6
ATOM	819	CE2	TYR	B	227	6.985	55.813	7.341	1.00	26.09	6
ATOM	820	CZ	TYR	B	227	5.634	55.910	7.543	1.00	23.78	6
ATOM	821	OH	TYR	B	227	5.113	57.191	7.727	1.00	28.18	8
ATOM	822	C	TYR	B	227	7.513	52.644	4.489	1.00	21.85	6
ATOM	823	O	TYR	B	227	6.545	53.199	3.930	1.00	27.43	8
ATOM	824	N	ASP	B	228	8.769	52.943	4.220	1.00	23.83	7
ATOM	825	CA	ASP	B	228	9.117	53.991	3.230	1.00	25.77	6
ATOM	826	CB	ASP	B	228	10.610	54.172	3.106	1.00	26.19	6
ATOM	827	CG	ASP	B	228	11.279	54.729	4.348	1.00	27.12	6
ATOM	828	OD1	ASP	B	228	10.518	55.146	5.256	1.00	28.17	8
ATOM	829	OD2	ASP	B	228	12.537	54.751	4.378	1.00	31.94	8
ATOM	830	C	ASP	B	228	8.519	53.695	1.862	1.00	25.92	6
ATOM	831	O	ASP	B	228	7.956	54.619	1.257	1.00	28.03	8
ATOM	832	N	GLN	B	229	8.540	52.452	1.469	1.00	27.73	7
ATOM	833	CA	GLN	B	229	7.956	52.045	0.199	1.00	31.06	6
ATOM	834	CB	GLN	B	229	8.436	50.632	−0.154	1.00	32.10	6
ATOM	835	CG	GLN	B	229	7.569	50.055	−1.271	1.00	40.19	6
ATOM	836	CD	GLN	B	229	8.063	48.701	−1.765	1.00	35.54	6
ATOM	837	OE1	GLN	B	229	7.397	47.704	−1.552	1.00	55.35	8
ATOM	838	NE2	GLN	B	229	9.228	48.759	−2.400	1.00	49.50	7
ATOM	839	C	GLN	B	229	6.462	52.183	0.174	1.00	29.95	6
ATOM	840	O	GLN	B	229	5.849	52.694	−0.755	1.00	30.54	8
ATOM	841	N	ALA	B	230	5.752	51.857	1.285	1.00	28.41	7
ATOM	842	CA	ALA	B	230	4.294	52.032	1.330	1.00	24.57	6
ATOM	843	CB	ALA	B	230	3.798	51.420	2.650	1.00	29.26	6
ATOM	844	C	ALA	B	230	3.929	53.503	1.291	1.00	27.29	6
ATOM	845	O	ALA	B	230	2.899	53.939	0.741	1.00	30.79	8
ATOM	846	N	LEU	B	231	4.736	54.350	1.937	1.00	24.06	7
ATOM	847	CA	LEU	B	231	4.454	55.788	1.977	1.00	26.67	6
ATOM	848	CB	LEU	B	231	5.489	56.473	2.816	1.00	33.38	6
ATOM	849	CG	LEU	B	231	5.296	57.803	3.506	1.00	35.20	6
ATOM	850	CD1	LEU	B	231	4.007	57.825	4.338	1.00	36.95	6
ATOM	851	CD2	LEU	B	231	6.470	57.979	4.478	1.00	30.01	6
ATOM	852	C	LEU	B	231	4.544	56.325	0.526	1.00	28.69	6
ATOM	853	O	LEU	B	231	3.664	57.109	0.174	1.00	32.37	8
ATOM	854	N	GLN	B	232	5.594	55.890	−0.151	1.00	28.25	7
ATOM	855	CA	GLN	B	232	5.788	56.301	−1.539	1.00	26.43	6
ATOM	856	CB	GLN	B	232	7.123	55.916	−2.154	1.00	27.83	6
ATOM	857	CG	GLN	B	232	7.104	56.319	−3.651	1.00	40.21	6
ATOM	858	CD	GLN	B	232	7.235	57.824	−3.813	1.00	44.86	6
ATOM	859	OE1	GLN	B	232	8.250	58.422	−3.452	1.00	47.98	8
ATOM	860	NE2	GLN	B	232	6.207	58.469	−4.365	1.00	59.78	7
ATOM	861	C	GLN	B	232	4.602	55.793	−2.328	1.00	32.25	6
ATOM	862	O	GLN	B	232	3.988	56.547	−3.078	1.00	34.60	8
ATOM	863	N	GLN	B	233	4.268	54.515	−2.235	1.00	30.14	7
ATOM	864	CA	GLN	B	233	3.120	53.953	−2.896	1.00	31.57	6
ATOM	865	CB	GLN	B	233	3.050	52.432	−2.787	1.00	36.28	6
ATOM	866	CG	GLN	B	233	4.251	51.705	−3.354	1.00	48.59	6
ATOM	867	CD	GLN	B	233	4.203	50.201	−3.105	1.00	57.17	6
ATOM	868	OE1	GLN	B	233	3.292	49.661	−2.475	1.00	55.45	8
ATOM	869	NE2	GLN	B	233	5.212	49.490	−3.609	1.00	52.72	7
ATOM	870	C	GLN	B	233	1.795	54.588	−2.597	1.00	36.59	6
ATOM	871	O	GLN	B	233	0.978	54.775	−3.490	1.00	33.24	8
ATOM	872	N	ALA	B	234	1.500	54.941	−1.342	1.00	34.08	7
ATOM	873	CA	ALA	B	234	0.236	55.543	−0.953	1.00	31.39	6
ATOM	874	CB	ALA	B	234	0.233	55.805	0.554	1.00	38.61	6
ATOM	875	C	ALA	B	234	−0.023	56.910	−1.579	1.00	37.11	6
ATOM	876	O	ALA	B	234	−1.162	57.369	−1.539	1.00	40.52	8
ATOM	877	N	VAL	B	235	1.020	57.582	−1.993	1.00	35.31	7
ATOM	878	CA	VAL	B	235	0.886	58.936	−2.523	1.00	45.20	6
ATOM	879	CB	VAL	B	235	2.237	59.674	−2.510	1.00	45.97	6
ATOM	880	CG1	VAL	B	235	2.240	60.797	−3.520	1.00	57.51	6
ATOM	881	CG2	VAL	B	235	2.552	60.112	−1.095	1.00	52.58	6
ATOM	882	C	VAL	B	235	0.303	58.949	−3.917	1.00	47.01	6
ATOM	883	O	VAL	B	235	−0.462	59.839	−4.250	1.00	44.05	8
ATOM	884	N	VAL	B	236	0.545	57.898	−4.675	1.00	53.53	7
ATOM	885	CA	VAL	B	236	0.086	57.778	−6.044	1.00	60.39	6
ATOM	886	CB	VAL	B	236	1.147	57.008	−6.861	1.00	61.99	6
ATOM	887	CG1	VAL	B	236	2.528	57.201	−6.254	1.00	60.20	6
ATOM	888	CG2	VAL	B	236	0.778	55.535	−6.904	1.00	55.70	6
ATOM	889	C	VAL	B	236	−1.253	57.088	−6.212	1.00	62.78	6
ATOM	890	O	VAL	B	236	−1.887	56.597	−5.282	1.00	63.95	8
ATOM	891	N	ASP	B	237	−1.720	57.051	−7.456	1.00	65.68	7
ATOM	892	CA	ASP	B	237	−2.972	56.428	−7.831	1.00	67.82	6
ATOM	893	CB	ASP	B	237	−2.741	54.984	−8.278	1.00	72.56	6
ATOM	894	CG	ASP	B	237	−2.597	54.853	−9.782	1.00	75.01	6
ATOM	895	OD1	ASP	B	237	−2.837	55.847	−10.500	1.00	71.57	8
ATOM	896	OD2	ASP	B	237	−2.249	53.743	−10.241	1.00	73.99	8
ATOM	897	C	ASP	B	237	−4.041	56.492	−6.756	1.00	67.93	6
ATOM	898	O	ASP	B	237	−3.990	57.440	−5.938	1.00	69.24	8
ATOM	899	CB	ASN	C	242	−2.832	47.036	−0.049	1.00	52.44	6
ATOM	900	CG	ASN	C	242	−3.531	46.708	1.256	1.00	53.59	6
ATOM	901	OD1	ASN	C	242	−4.754	46.644	1.309	1.00	68.85	8
ATOM	902	ND2	ASN	C	242	−2.755	46.521	2.306	1.00	62.22	7
ATOM	903	C	ASN	C	242	−2.213	49.417	0.387	1.00	39.79	6
ATOM	904	O	ASN	C	242	−2.332	49.370	1.630	1.00	39.72	8
ATOM	905	N	ASN	C	242	−3.171	48.676	−1.871	1.00	39.76	7
ATOM	906	CA	ASN	C	242	−3.103	48.497	−0.415	1.00	43.08	6
ATOM	907	N	ALA	C	243	−1.401	50.254	−0.254	1.00	36.60	7
ATOM	908	CA	ALA	C	243	−0.491	51.133	0.430	1.00	34.21	6
ATOM	909	CB	ALA	C	243	0.480	51.825	−0.534	1.00	32.11	6
ATOM	910	C	ALA	C	243	−1.151	52.133	1.366	1.00	36.65	6
ATOM	911	O	ALA	C	243	−0.621	52.349	2.471	1.00	33.63	8
ATOM	912	N	LYS	C	244	−2.309	52.694	0.990	1.00	31.22	7
ATOM	913	CA	LYS	C	244	−2.931	53.638	1.903	1.00	35.12	6
ATOM	914	CB	LYS	C	244	−4.102	54.402	1.304	1.00	38.30	6
ATOM	915	CG	LYS	C	244	−3.677	55.244	0.096	1.00	47.69	6
ATOM	916	CD	LYS	C	244	−4.704	56.314	−0.233	1.00	59.26	6
ATOM	917	CE	LYS	C	244	−4.248	57.259	−1.342	1.00	45.56	6
ATOM	918	NZ	LYS	C	244	−3.736	56.493	−2.515	1.00	48.06	7
ATOM	919	C	LYS	C	244	−3.251	52.942	3.219	1.00	31.26	6
ATOM	920	O	LYS	C	244	−3.045	53.522	4.294	1.00	37.97	8
ATOM	921	N	ALA	C	245	−3.851	51.759	3.155	1.00	35.96	7
ATOM	922	CA	ALA	C	245	−4.202	51.044	4.371	1.00	35.05	6
ATOM	923	CB	ALA	C	245	−5.204	49.931	4.208	1.00	37.25	6
ATOM	924	C	ALA	C	245	−2.983	50.617	5.184	1.00	32.82	6
ATOM	925	O	ALA	C	245	−3.059	50.740	6.420	1.00	29.94	8
ATOM	926	N	VAL	C	246	−1.907	50.246	4.499	1.00	33.79	7
ATOM	927	CA	VAL	C	246	−0.705	49.866	5.266	1.00	29.90	6
ATOM	928	CB	VAL	C	246	0.366	49.269	4.369	1.00	29.88	6
ATOM	929	CG1	VAL	C	246	0.056	47.917	3.771	1.00	34.43	6
ATOM	930	CG2	VAL	C	246	1.773	49.346	4.931	1.00	29.74	6
ATOM	931	C	VAL	C	246	−0.168	51.083	5.984	1.00	30.62	6
ATOM	932	O	VAL	C	246	0.208	51.067	7.166	1.00	29.83	8
ATOM	933	N	VAL	C	247	−0.095	52.225	5.269	1.00	28.26	7
ATOM	934	CA	VAL	C	247	0.348	53.468	5.911	1.00	25.89	6
ATOM	935	CB	VAL	C	247	0.316	54.634	4.873	1.00	32.16	6
ATOM	936	CG1	VAL	C	247	0.468	55.966	5.600	1.00	29.03	6
ATOM	937	CG2	VAL	C	247	1.529	54.419	3.961	1.00	37.46	6
ATOM	938	C	VAL	C	247	−0.533	53.832	7.100	1.00	28.13	6
ATOM	939	O	VAL	C	247	−0.035	54.171	8.176	1.00	27.03	8
ATOM	940	N	LYS	C	248	−1.851	53.790	6.935	1.00	25.46	7
ATOM	941	CA	LYS	C	248	−2.739	54.143	8.033	1.00	28.62	6
ATOM	942	CB	LYS	C	248	−4.215	54.072	7.623	1.00	41.92	6
ATOM	943	CG	LYS	C	248	−5.117	54.460	8.801	1.00	55.47	6
ATOM	944	CD	LYS	C	248	−6.509	53.868	8.678	1.00	53.90	6
ATOM	945	CE	LYS	C	248	−7.538	54.663	9.470	1.00	57.26	6
ATOM	946	NZ	LYS	C	248	−7.729	56.016	8.867	1.00	64.95	7
ATOM	947	C	LYS	C	248	−2.548	53.220	9.240	1.00	27.15	6
ATOM	948	O	LYS	C	248	−2.552	53.715	10.363	1.00	27.05	8
ATOM	949	N	THR	C	249	−2.356	51.947	8.963	1.00	27.77	7
ATOM	950	CA	THR	C	249	−2.134	50.940	9.998	1.00	25.68	6
ATOM	951	CB	THR	C	249	−2.085	49.544	9.335	1.00	32.70	6
ATOM	952	OG1	THR	C	249	−3.453	49.231	8.992	1.00	33.92	8
ATOM	953	CG2	THR	C	249	−1.680	48.496	10.385	1.00	28.13	6
ATOM	954	C	THR	C	249	−0.862	51.225	10.734	1.00	21.92	6
ATOM	955	O	THR	C	249	−0.862	51.153	11.973	1.00	26.37	8
ATOM	956	N	PHE	C	250	0.224	51.510	10.052	1.00	24.01	7
ATOM	957	CA	PHE	C	250	1.452	51.874	10.753	1.00	22.16	6
ATOM	958	CB	PHE	C	250	2.617	51.986	9.764	1.00	23.90	6
ATOM	959	CG	PHE	C	250	3.359	50.719	9.523	1.00	20.12	6
ATOM	960	CD1	PHE	C	250	2.740	49.629	8.943	1.00	26.67	6
ATOM	961	CD2	PHE	C	250	4.703	50.639	9.883	1.00	24.12	6
ATOM	962	CE1	PHE	C	250	3.448	48.448	8.753	1.00	25.84	6
ATOM	963	CE2	PHE	C	250	5.393	49.449	9.704	1.00	26.95	6
ATOM	964	CZ	PHE	C	250	4.788	48.377	9.098	1.00	26.24	6
ATOM	965	C	PHE	C	250	1.272	53.105	11.613	1.00	23.98	6
ATOM	966	O	PHE	C	250	1.713	53.163	12.779	1.00	23.60	8
ATOM	967	N	HIS	C	251	0.654	54.143	11.040	1.00	23.00	7
ATOM	968	CA	HIS	C	251	0.506	55.406	11.779	1.00	24.29	6
ATOM	969	CB	HIS	C	251	−0.108	56.474	10.895	1.00	28.22	6
ATOM	970	CG	HIS	C	251	0.848	56.857	9.809	1.00	22.07	6
ATOM	971	CD2	HIS	C	251	2.172	56.586	9.687	1.00	20.33	6
ATOM	972	ND1	HIS	C	251	0.474	57.604	8.733	1.00	27.95	7
ATOM	973	CE1	HIS	C	251	1.546	57.774	7.977	1.00	24.46	6
ATOM	974	NE2	HIS	C	251	2.594	57.162	8.476	1.00	23.12	7
ATOM	975	C	HIS	C	251	−0.307	55.195	13.030	1.00	20.90	6
ATOM	976	O	HIS	C	251	0.070	55.675	14.085	1.00	27.74	8
ATOM	977	N	GLU	C	252	−1.409	54.479	12.901	1.00	24.95	7
ATOM	978	CA	GLU	C	252	−2.287	54.246	14.059	1.00	28.46	6
ATOM	979	CB	GLU	C	252	−3.544	53.531	13.532	1.00	33.82	6
ATOM	980	CG	GLU	C	252	−4.584	54.560	13.085	1.00	50.99	6
ATOM	981	CD	GLU	C	252	−5.218	55.177	14.320	1.00	58.60	6
ATOM	982	OE1	GLU	C	252	−5.078	54.538	15.384	1.00	71.21	8
ATOM	983	OE2	GLU	C	252	−5.827	56.258	14.217	1.00	74.51	8
ATOM	984	C	GLU	C	252	−1.649	53.320	15.076	1.00	25.23	6
ATOM	985	O	GLU	C	252	−1.725	53.623	16.292	1.00	27.62	8
ATOM	986	N	THR	C	253	−0.948	52.285	14.608	1.00	24.22	7
ATOM	987	CA	THR	C	253	−0.336	51.351	15.541	1.00	25.24	6
ATOM	988	CB	THR	C	253	0.122	50.084	14.769	1.00	30.19	6
ATOM	989	OG1	THR	C	253	−1.087	49.511	14.236	1.00	29.93	8
ATOM	990	CG2	THR	C	253	0.659	49.055	15.758	1.00	29.01	6
ATOM	991	C	THR	C	253	0.830	51.942	16.282	1.00	26.99	6
ATOM	992	O	THR	C	253	0.987	51.670	17.488	1.00	26.85	8
ATOM	993	N	LEU	C	254	1.663	52.716	15.590	1.00	25.36	7
ATOM	994	CA	LEU	C	254	2.892	53.221	16.188	1.00	25.88	6
ATOM	995	CB	LEU	C	254	4.109	53.104	15.238	1.00	26.52	6
ATOM	996	CG	LEU	C	254	4.359	51.782	14.532	1.00	28.64	6
ATOM	997	CD1	LEU	C	254	5.319	51.868	13.356	1.00	26.29	6
ATOM	998	CD2	LEU	C	254	4.785	50.714	15.546	1.00	31.46	6
ATOM	999	C	LEU	C	254	2.771	54.634	16.713	1.00	23.22	6
ATOM	1000	O	LEU	C	254	3.703	55.129	17.323	1.00	29.91	8
ATOM	1001	N	ASP	C	255	1.650	55.306	16.425	1.00	26.04	7
ATOM	1002	CA	ASP	C	255	1.388	56.653	16.899	1.00	28.87	6
ATOM	1003	CB	ASP	C	255	1.580	56.705	18.457	1.00	27.97	6
ATOM	1004	CG	ASP	C	255	0.731	57.830	19.007	1.00	38.75	6
ATOM	1005	OD1	ASP	C	255	−0.377	58.016	18.460	1.00	39.85	8
ATOM	1006	OD2	ASP	C	255	1.167	58.483	19.981	1.00	49.40	8
ATOM	1007	C	ASP	C	255	2.398	57.629	16.324	1.00	26.53	6
ATOM	1008	O	ASP	C	255	3.180	58.334	16.965	1.00	30.14	8
ATOM	1009	N	CYS	C	256	2.413	57.598	14.957	1.00	23.58	7
ATOM	1010	CA	CYS	C	256	3.298	58.532	14.225	1.00	23.99	6
ATOM	1011	C	CYS	C	256	2.648	58.853	12.873	1.00	23.60	6
ATOM	1012	O	CYS	C	256	1.527	58.447	12.512	1.00	25.41	8
ATOM	1013	CB	CYS	C	256	4.637	57.834	13.913	1.00	27.13	6
ATOM	1014	SG	CYS	C	256	4.516	56.303	12.969	1.00	25.36	16
ATOM	1015	N	CYS	C	257	3.385	59.714	12.151	1.00	24.12	7
ATOM	1016	CA	CYS	C	257	2.892	60.177	10.853	1.00	23.16	6
ATOM	1017	C	CYS	C	257	4.139	60.542	10.014	1.00	24.72	6
ATOM	1018	O	CYS	C	257	4.847	61.504	10.308	1.00	35.05	8
ATOM	1019	CB	CYS	C	257	2.010	61.419	11.084	1.00	25.12	6
ATOM	1020	SG	CYS	C	257	1.467	62.126	9.517	1.00	38.79	16
ATOM	1021	N	GLY	C	258	4.489	59.747	9.012	1.00	28.13	7
ATOM	1022	CA	GLY	C	258	5.588	60.028	8.166	1.00	29.38	6
ATOM	1023	C	GLY	C	258	6.986	59.897	8.749	1.00	27.80	6
ATOM	1024	O	GLY	C	258	7.302	59.270	9.763	1.00	27.20	8
ATOM	1025	N	SER	C	259	7.907	60.517	7.979	1.00	23.88	7
ATOM	1026	CA	SER	C	259	9.319	60.378	8.276	1.00	24.44	6
ATOM	1027	CB	SER	C	259	9.939	59.307	7.342	1.00	24.84	6
ATOM	1028	OG	SER	C	259	11.346	59.213	7.645	1.00	24.95	8
ATOM	1029	C	SER	C	259	10.034	61.697	8.068	1.00	23.27	6
ATOM	1030	O	SER	C	259	9.868	62.267	6.973	1.00	25.69	8
ATOM	1031	N	SER	C	260	10.980	62.031	8.914	1.00	23.41	7
ATOM	1032	CA	SER	C	260	11.848	63.181	8.666	1.00	26.33	6
ATOM	1033	CB	SER	C	260	12.884	63.261	9.785	1.00	27.51	6
ATOM	1034	OG	SER	C	260	12.179	63.570	10.989	1.00	28.13	8
ATOM	1035	C	SER	C	260	12.676	63.039	7.371	1.00	29.57	6
ATOM	1036	O	SER	C	260	13.077	64.066	6.849	1.00	30.79	8
ATOM	1037	N	THR	C	261	12.896	61.841	6.873	1.00	26.07	7
ATOM	1038	CA	THR	C	261	13.692	61.604	5.669	1.00	27.09	6
ATOM	1039	CB	THR	C	261	14.272	60.165	5.682	1.00	33.47	6
ATOM	1040	OG1	THR	C	261	13.261	59.151	5.651	1.00	27.38	8
ATOM	1041	CG2	THR	C	261	15.173	59.975	6.879	1.00	32.39	6
ATOM	1042	C	THR	C	261	12.864	61.784	4.414	1.00	28.01	6
ATOM	1043	O	THR	C	261	13.421	61.744	3.288	1.00	30.80	8
ATOM	1044	N	LEU	C	262	11.552	61.893	4.543	1.00	24.40	7
ATOM	1045	CA	LEU	C	262	10.639	61.952	3.428	1.00	25.43	6
ATOM	1046	CB	LEU	C	262	9.914	60.611	3.138	1.00	28.21	6
ATOM	1047	CG	LEU	C	262	10.883	59.510	2.708	1.00	26.53	6
ATOM	1048	CD1	LEU	C	262	10.350	58.121	2.895	1.00	30.08	6
ATOM	1049	CD2	LEU	C	262	11.259	59.683	1.219	1.00	28.90	6
ATOM	1050	C	LEU	C	262	9.616	63.049	3.657	1.00	23.19	6
ATOM	1051	O	LEU	C	262	8.439	62.766	3.792	1.00	26.41	8
ATOM	1052	N	THR	C	263	10.094	64.280	3.767	1.00	26.39	7
ATOM	1053	CA	THR	C	263	9.161	65.386	4.059	1.00	27.72	6
ATOM	1054	CB	THR	C	263	9.896	66.696	4.405	1.00	25.97	6
ATOM	1055	OG1	THR	C	263	10.729	66.986	3.282	1.00	30.14	8
ATOM	1056	CG2	THR	C	263	10.827	66.427	5.589	1.00	27.82	6
ATOM	1057	C	THR	C	263	8.032	65.629	3.102	1.00	26.70	6
ATOM	1058	O	THR	C	263	6.878	65.844	3.504	1.00	28.71	8
ATOM	1059	N	ALA	C	264	8.304	65.522	1.773	1.00	26.68	7
ATOM	1060	CA	ALA	C	264	7.204	65.683	0.833	1.00	28.81	6
ATOM	1061	CB	ALA	C	264	7.792	65.684	−0.583	1.00	37.35	6
ATOM	1062	C	ALA	C	264	6.131	64.613	0.943	1.00	29.88	6
ATOM	1063	O	ALA	C	264	4.928	64.893	0.823	1.00	27.29	8
ATOM	1064	N	LEU	C	265	6.556	63.336	1.110	1.00	26.34	7
ATOM	1065	CA	LEU	C	265	5.538	62.287	1.253	1.00	25.11	6
ATOM	1066	CB	LEU	C	265	6.196	60.887	1.270	1.00	28.31	6
ATOM	1067	CG	LEU	C	265	6.907	60.588	−0.062	1.00	29.73	6
ATOM	1068	CD1	LEU	C	265	7.569	59.240	0.095	1.00	33.59	6
ATOM	1069	CD2	LEU	C	265	5.839	60.531	−1.146	1.00	28.63	6
ATOM	1070	C	LEU	C	265	4.751	62.425	2.549	1.00	23.39	6
ATOM	1071	O	LEU	C	265	3.559	62.162	2.563	1.00	26.66	8
ATOM	1072	N	THR	C	266	5.439	63.023	3.542	1.00	25.29	7
ATOM	1073	CA	THR	C	266	4.716	63.271	4.808	1.00	22.08	6
ATOM	1074	CB	THR	C	266	5.727	63.729	5.881	1.00	23.25	6
ATOM	1075	OG1	THR	C	266	6.648	62.625	6.056	1.00	25.07	8
ATOM	1076	CG2	THR	C	266	5.058	63.990	7.240	1.00	23.91	6
ATOM	1077	C	THR	C	266	3.654	64.375	4.578	1.00	22.75	6
ATOM	1078	O	THR	C	266	2.556	64.260	5.081	1.00	28.42	8
ATOM	1079	N	THR	C	267	4.040	65.386	3.793	1.00	25.87	7
ATOM	1080	CA	THR	C	267	3.019	66.421	3.509	1.00	26.21	6
ATOM	1081	CB	THR	C	267	3.635	67.461	2.586	1.00	28.25	6
ATOM	1082	OG1	THR	C	267	4.745	68.101	3.197	1.00	28.51	8
ATOM	1083	CG2	THR	C	267	2.581	68.472	2.123	1.00	27.94	6
ATOM	1084	C	THR	C	267	1.818	65.733	2.855	1.00	27.78	6
ATOM	1085	O	THR	C	267	0.690	65.985	3.208	1.00	29.01	8
ATOM	1086	N	SER	C	268	2.094	64.819	1.906	1.00	27.61	7
ATOM	1087	CA	SER	C	268	0.979	64.143	1.229	1.00	25.35	6
ATOM	1088	CB	SER	C	268	1.548	63.536	−0.058	1.00	32.95	6
ATOM	1089	OG	SER	C	268	0.564	62.685	−0.630	1.00	44.07	8
ATOM	1090	C	SER	C	268	0.101	63.347	2.138	1.00	30.80	6
ATOM	1091	O	SER	C	268	−1.147	63.435	2.174	1.00	33.02	8
ATOM	1092	N	VAL	C	269	0.728	62.580	3.065	1.00	27.58	7
ATOM	1093	CA	VAL	C	269	−0.081	61.844	4.023	1.00	34.13	6
ATOM	1094	CB	VAL	C	269	0.621	60.665	4.655	1.00	38.22	6
ATOM	1095	CG1	VAL	C	269	0.872	59.601	3.584	1.00	45.09	6
ATOM	1096	CG2	VAL	C	269	1.899	61.022	5.375	1.00	44.36	6
ATOM	1097	C	VAL	C	269	−0.922	62.762	4.888	1.00	30.87	6
ATOM	1098	O	VAL	C	269	−2.068	62.347	5.141	1.00	33.47	8
ATOM	1099	N	LEU	C	270	−0.426	63.946	5.266	1.00	28.56	7
ATOM	1100	CA	LEU	C	270	−1.285	64.827	6.067	1.00	30.65	6
ATOM	1101	CB	LEU	C	270	−0.460	66.044	6.549	1.00	36.56	6
ATOM	1102	CG	LEU	C	270	0.538	65.662	7.647	1.00	34.36	6
ATOM	1103	CD1	LEU	C	270	1.529	66.803	7.862	1.00	41.70	6
ATOM	1104	CD2	LEU	C	270	−0.232	65.408	8.925	1.00	35.94	6
ATOM	1105	C	LEU	C	270	−2.396	65.387	5.189	1.00	33.16	6
ATOM	1106	O	LEU	C	270	−3.505	65.574	5.686	1.00	45.89	8
ATOM	1107	N	LYS	C	271	−2.124	65.660	3.938	1.00	34.32	7
ATOM	1108	CA	LYS	C	271	−3.134	66.246	3.050	1.00	41.10	6
ATOM	1109	CB	LYS	C	271	−2.472	66.769	1.783	1.00	32.67	6
ATOM	1110	CG	LYS	C	271	−2.127	68.233	1.717	1.00	43.61	6
ATOM	1111	CD	LYS	C	271	−0.952	68.551	0.830	1.00	50.73	6
ATOM	1112	CE	LYS	C	271	−1.260	69.015	−0.572	1.00	54.10	6
ATOM	1113	NZ	LYS	C	271	−0.039	69.130	−1.431	1.00	56.13	7
ATOM	1114	C	LYS	C	271	−4.193	65.214	2.672	1.00	46.38	6
ATOM	1115	O	LYS	C	271	−5.236	65.554	2.114	1.00	47.27	8
ATOM	1116	N	ASN	C	272	−3.879	63.946	2.880	1.00	45.09	7
ATOM	1117	CA	ASN	C	272	−4.778	62.853	2.522	1.00	43.41	6
ATOM	1118	CB	ASN	C	272	−4.086	61.857	1.593	1.00	50.61	6
ATOM	1119	CG	ASN	C	272	−3.723	62.457	0.250	1.00	49.74	6
ATOM	1120	OD1	ASN	C	272	−2.963	61.847	−0.503	1.00	60.30	8
ATOM	1121	ND2	ASN	C	272	−4.256	63.636	−0.037	1.00	52.35	7
ATOM	1122	C	ASN	C	272	−5.367	62.117	3.710	1.00	42.86	6
ATOM	1123	O	ASN	C	272	−5.855	60.989	3.575	1.00	42.83	8
ATOM	1124	N	ASN	C	273	−5.378	62.712	4.895	1.00	42.22	7
ATOM	1125	CA	ASN	C	273	−5.956	62.073	6.073	1.00	44.58	6
ATOM	1126	CB	ASN	C	273	−7.465	62.188	6.138	1.00	52.14	6
ATOM	1127	CG	ASN	C	273	−8.169	61.943	7.449	1.00	66.60	6
ATOM	1128	OD1	ASN	C	273	−9.311	61.452	7.442	1.00	61.59	8
ATOM	1129	ND2	ASN	C	273	−7.599	62.249	8.609	1.00	53.47	7
ATOM	1130	C	ASN	C	273	−5.447	60.654	6.272	1.00	44.46	6
ATOM	1131	O	ASN	C	273	−6.213	59.729	6.565	1.00	42.25	8
ATOM	1132	N	LEU	C	274	−4.120	60.506	6.183	1.00	33.07	7
ATOM	1133	CA	LEU	C	274	−3.513	59.186	6.407	1.00	37.06	6
ATOM	1134	CB	LEU	C	274	−2.550	58.789	5.288	1.00	33.35	6
ATOM	1135	CG	LEU	C	274	−3.171	58.526	3.908	1.00	36.17	6
ATOM	1136	CD1	LEU	C	274	−2.201	58.059	2.854	1.00	35.69	6
ATOM	1137	CD2	LEU	C	274	−4.292	57.498	4.023	1.00	42.68	6
ATOM	1138	C	LEU	C	274	−2.827	59.212	7.772	1.00	35.03	6
ATOM	1139	O	LEU	C	274	−2.224	58.213	8.172	1.00	39.17	8
ATOM	1140	N	CYS	C	275	−3.049	60.262	8.549	1.00	34.81	7
ATOM	1141	CA	CYS	C	275	−2.477	60.330	9.886	1.00	36.93	6
ATOM	1142	C	CYS	C	275	−3.551	60.482	10.979	1.00	41.89	6
ATOM	1143	O	CYS	C	275	−4.507	61.231	10.816	1.00	42.44	8
ATOM	1144	CB	CYS	C	275	−1.450	61.458	9.952	1.00	37.22	6
ATOM	1145	SG	CYS	C	275	0.032	61.171	8.939	1.00	40.09	16
ATOM	1146	N	PRO	C	276	−3.307	59.747	12.085	1.00	43.00	7
ATOM	1147	CD	PRO	C	276	−2.168	58.833	12.246	1.00	46.79	6
ATOM	1148	CA	PRO	C	276	−4.227	59.720	13.270	1.00	45.18	6
ATOM	1149	CB	PRO	C	276	−3.501	58.834	14.281	1.00	43.00	6
ATOM	1150	CG	PRO	C	276	−2.108	58.658	13.734	1.00	44.89	6
ATOM	1151	C	PRO	C	276	−4.522	61.074	13.906	1.00	44.90	6
ATOM	1152	O	PRO	C	276	−3.683	61.964	13.848	1.00	40.22	8
ATOM	1153	N	SER	C	277	−5.702	61.239	14.523	1.00	49.31	7
ATOM	1154	CA	SER	C	277	−6.057	62.560	15.080	1.00	53.44	6
ATOM	1155	CB	SER	C	277	−7.590	62.750	15.034	1.00	61.29	6
ATOM	1156	OG	SER	C	277	−7.984	63.864	15.817	1.00	59.45	8
ATOM	1157	C	SER	C	277	−5.531	62.914	16.533	1.00	56.84	6
ATOM	1158	O	SER	C	277	−6.323	63.093	17.457	1.00	58.71	8
ATOM	1159	N	GLY	C	278	−4.196	63.036	16.701	0.00	72.91	7
ATOM	1160	CA	GLY	C	278	−3.535	63.382	17.979	0.00	72.16	6
ATOM	1161	C	GLY	C	278	−2.623	64.645	17.863	0.00	71.11	6
ATOM	1162	O	GLY	C	278	−1.651	64.671	17.108	0.00	72.04	8
ATOM	1163	N	GLY	C	279	−3.014	65.688	18.600	0.00	67.96	7
ATOM	1164	CA	GLY	C	279	−2.296	66.962	18.676	0.00	66.01	6
ATOM	1165	C	GLY	C	279	−0.889	66.636	19.187	0.00	61.41	6
ATOM	1166	O	GLY	C	279	0.045	67.424	19.020	0.00	60.21	8
ATOM	1167	N	ASN	C	280	−0.768	65.439	19.816	0.00	43.63	7
ATOM	1168	CA	ASN	C	280	0.471	64.860	20.274	1.00	41.26	6
ATOM	1169	CB	ASN	C	280	0.281	63.676	21.248	1.00	51.58	6
ATOM	1170	CG	ASN	C	280	1.538	62.874	21.591	1.00	65.06	6
ATOM	1171	OD1	ASN	C	280	2.201	63.121	22.603	1.00	62.58	8
ATOM	1172	ND2	ASN	C	280	1.863	61.923	20.739	1.00	69.23	7
ATOM	1173	C	ASN	C	280	1.134	64.414	19.000	1.00	39.27	6
ATOM	1174	O	ASN	C	280	2.367	64.438	18.861	1.00	43.66	8
ATOM	1175	N	ILE	C	281	0.309	63.983	18.044	1.00	37.18	7
ATOM	1176	CA	ILE	C	281	0.909	63.540	16.783	1.00	39.37	6
ATOM	1177	CB	ILE	C	281	−0.106	62.955	15.765	1.00	35.78	6
ATOM	1178	CG2	ILE	C	281	0.541	62.824	14.398	1.00	53.65	6
ATOM	1179	CG1	ILE	C	281	−0.652	61.595	16.245	1.00	34.01	6
ATOM	1180	CD1	ILE	C	281	0.391	60.510	16.337	1.00	39.13	6
ATOM	1181	C	ILE	C	281	1.619	64.698	16.132	1.00	37.32	6
ATOM	1182	O	ILE	C	281	2.790	64.607	15.753	1.00	37.87	8
ATOM	1183	N	ILE	C	282	0.906	65.826	16.001	1.00	29.62	7
ATOM	1184	CA	ILE	C	282	1.445	66.989	15.332	1.00	29.15	6
ATOM	1185	CB	ILE	C	282	0.318	68.006	15.057	1.00	29.10	6
ATOM	1186	CG2	ILE	C	282	0.792	69.228	14.292	1.00	33.23	6
ATOM	1187	CG1	ILE	C	282	−0.887	67.372	14.382	1.00	37.23	6
ATOM	1188	CD1	ILE	C	282	−0.521	66.651	13.108	1.00	39.06	6
ATOM	1189	C	ILE	C	282	2.622	67.555	16.086	1.00	27.74	6
ATOM	1190	O	ILE	C	282	3.616	67.958	15.470	1.00	27.48	8
ATOM	1191	N	SER	C	283	2.536	67.671	17.429	1.00	31.63	7
ATOM	1192	CA	SER	C	283	3.632	68.234	18.186	1.00	28.41	6
ATOM	1193	CB	SER	C	283	3.217	68.521	19.632	1.00	37.49	6
ATOM	1194	OG	SER	C	283	3.292	67.403	20.469	1.00	52.68	8
ATOM	1195	C	SER	C	283	4.900	67.401	18.084	1.00	30.27	6
ATOM	1196	O	SER	C	283	6.003	67.938	18.285	1.00	30.36	8
ATOM	1197	N	ASN	C	284	4.773	66.116	17.783	1.00	26.22	7
ATOM	1198	CA	ASN	C	284	5.959	65.269	17.620	1.00	27.42	6
ATOM	1199	CB	ASN	C	284	5.744	64.023	18.532	1.00	29.26	6
ATOM	1200	CG	ASN	C	284	5.959	64.586	19.955	1.00	36.37	6
ATOM	1201	OD1	ASN	C	284	7.018	65.179	20.173	1.00	34.52	8
ATOM	1202	ND2	ASN	C	284	4.959	64.417	20.770	1.00	39.70	7
ATOM	1203	C	ASN	C	284	6.060	64.717	16.192	1.00	22.07	6
ATOM	1204	O	ASN	C	284	6.730	63.711	15.988	1.00	27.09	8
ATOM	1205	N	LEU	C	285	5.436	65.408	15.232	1.00	25.57	7
ATOM	1206	CA	LEU	C	285	5.477	64.935	13.835	1.00	24.22	6
ATOM	1207	CB	LEU	C	285	5.021	66.064	12.899	1.00	28.37	6
ATOM	1208	CG	LEU	C	285	5.034	65.744	11.397	1.00	27.69	6
ATOM	1209	CD1	LEU	C	285	4.105	64.552	11.189	1.00	27.75	6
ATOM	1210	CD2	LEU	C	285	4.488	66.992	10.655	1.00	24.39	6
ATOM	1211	C	LEU	C	285	6.822	64.396	13.386	1.00	28.96	6
ATOM	1212	O	LEU	C	285	6.917	63.272	12.850	1.00	26.23	8
ATOM	1213	N	PHE	C	286	7.891	65.192	13.539	1.00	25.55	7
ATOM	1214	CA	PHE	C	286	9.221	64.787	13.177	1.00	23.44	6
ATOM	1215	CB	PHE	C	286	9.906	65.839	12.290	1.00	23.03	6
ATOM	1216	CG	PHE	C	286	9.199	65.986	10.955	1.00	20.67	6
ATOM	1217	CD1	PHE	C	286	8.607	67.187	10.626	1.00	23.30	6
ATOM	1218	CD2	PHE	C	286	9.115	64.917	10.076	1.00	24.24	6
ATOM	1219	CE1	PHE	C	286	7.950	67.339	9.417	1.00	28.29	6
ATOM	1220	CE2	PHE	C	286	8.487	65.083	8.856	1.00	25.76	6
ATOM	1221	CZ	PHE	C	286	7.926	66.293	8.495	1.00	25.94	6
ATOM	1222	C	PHE	C	286	10.085	64.498	14.414	1.00	24.30	6
ATOM	1223	O	PHE	C	286	11.143	63.917	14.225	1.00	28.00	8
ATOM	1224	N	LYS	C	287	9.635	64.960	15.579	1.00	25.79	7
ATOM	1225	CA	LYS	C	287	10.472	64.671	16.761	1.00	28.66	6
ATOM	1226	CB	LYS	C	287	9.975	65.378	18.014	1.00	30.74	6
ATOM	1227	CG	LYS	C	287	10.046	66.886	17.851	1.00	39.07	6
ATOM	1228	CD	LYS	C	287	9.564	67.582	19.120	1.00	37.66	6
ATOM	1229	CE	LYS	C	287	10.235	67.045	20.364	1.00	44.51	6
ATOM	1230	NZ	LYS	C	287	9.589	67.630	21.579	1.00	51.78	7
ATOM	1231	C	LYS	C	287	10.393	63.163	17.058	1.00	27.32	6
ATOM	1232	O	LYS	C	287	11.378	62.681	17.638	1.00	32.08	8
ATOM	1233	N	GLU	C	288	9.262	62.558	16.853	1.00	25.65	7
ATOM	1234	CA	GLU	C	288	9.168	61.109	17.057	1.00	26.38	6
ATOM	1235	CB	GLU	C	288	8.405	60.799	18.330	1.00	32.61	6
ATOM	1236	CG	GLU	C	288	8.883	61.580	19.545	1.00	35.86	6
ATOM	1237	CD	GLU	C	288	7.953	61.282	20.715	1.00	49.68	6
ATOM	1238	OE1	GLU	C	288	7.772	62.105	21.631	1.00	55.75	8
ATOM	1239	OE2	GLU	C	288	7.361	60.177	20.724	1.00	63.52	8
ATOM	1240	C	GLU	C	288	8.424	60.477	15.876	1.00	24.79	6
ATOM	1241	O	GLU	C	288	7.289	60.032	15.983	1.00	25.16	8
ATOM	1242	N	ASP	C	289	9.125	60.434	14.753	1.00	26.85	7
ATOM	1243	CA	ASP	C	289	8.568	59.980	13.508	1.00	24.56	6
ATOM	1244	CB	ASP	C	289	9.369	60.684	12.398	1.00	25.50	6
ATOM	1245	CG	ASP	C	289	10.715	60.115	12.072	1.00	27.35	6
ATOM	1246	OD1	ASP	C	289	11.562	60.768	11.372	1.00	26.87	8
ATOM	1247	OD2	ASP	C	289	11.060	58.983	12.489	1.00	26.73	8
ATOM	1248	C	ASP	C	289	8.519	58.474	13.355	1.00	25.27	6
ATOM	1249	O	ASP	C	289	8.888	57.761	14.315	1.00	24.29	8
ATOM	1250	N	CYS	C	290	7.889	57.995	12.292	1.00	22.72	7
ATOM	1251	CA	CYS	C	290	7.722	56.512	12.197	1.00	21.85	6
ATOM	1252	C	CYS	C	290	9.039	55.781	12.183	1.00	23.09	6
ATOM	1253	O	CYS	C	290	8.987	54.628	12.645	1.00	24.17	8
ATOM	1254	CB	CYS	C	290	6.862	56.136	11.009	1.00	26.13	6
ATOM	1255	SG	CYS	C	290	5.240	56.851	11.104	1.00	24.30	16
ATOM	1256	N	HIS	C	291	10.181	56.308	11.712	1.00	21.89	7
ATOM	1257	CA	HIS	C	291	11.421	55.547	11.830	1.00	19.74	6
ATOM	1258	CB	HIS	C	291	12.547	56.294	11.070	1.00	25.39	6
ATOM	1259	CG	HIS	C	291	12.326	56.132	9.596	1.00	23.25	6
ATOM	1260	CD2	HIS	C	291	11.317	55.748	8.792	1.00	26.31	6
ATOM	1261	ND1	HIS	C	291	13.423	56.382	8.784	1.00	27.59	7
ATOM	1262	CE1	HIS	C	291	13.078	56.155	7.514	1.00	30.34	6
ATOM	1263	NE2	HIS	C	291	11.831	55.757	7.489	1.00	25.82	7
ATOM	1264	C	HIS	C	291	11.759	55.412	13.318	1.00	22.34	6
ATOM	1265	O	HIS	C	291	12.280	54.354	13.735	1.00	25.37	8
ATOM	1266	N	GLN	C	292	11.615	56.518	14.052	1.00	20.97	7
ATOM	1267	CA	GLN	C	292	11.899	56.386	15.511	1.00	21.60	6
ATOM	1268	CB	GLN	C	292	11.760	57.772	16.145	1.00	27.40	6
ATOM	1269	CG	GLN	C	292	12.000	57.661	17.656	1.00	28.40	6
ATOM	1270	CD	GLN	C	292	13.484	57.430	17.859	1.00	32.24	6
ATOM	1271	QE1	GLN	C	292	14.393	58.103	17.336	1.00	39.00	8
ATOM	1272	NE2	GLN	C	292	13.874	56.455	18.679	1.00	35.20	7
ATOM	1273	C	GLN	C	292	10.977	55.406	16.173	1.00	22.96	6
ATOM	1274	O	GLN	C	292	11.439	54.599	17.005	1.00	25.46	8
ATOM	1275	N	LYS	C	293	9.706	55.391	15.844	1.00	20.49	7
ATOM	1276	CA	LYS	C	293	8.766	54.437	16.454	1.00	24.11	6
ATOM	1277	CB	LYS	C	293	7.316	54.705	16.123	1.00	21.49	6
ATOM	1278	CG	LYS	C	293	6.906	56.132	16.541	1.00	20.82	6
ATOM	1279	CD	LYS	C	293	7.166	56.246	18.080	1.00	26.19	6
ATOM	1280	CE	LYS	C	293	6.380	57.510	18.465	1.00	31.71	6
ATOM	1281	NZ	LYS	C	293	6.412	57.682	19.953	1.00	43.53	7
ATOM	1282	C	LYS	C	293	9.094	52.995	16.091	1.00	24.90	6
ATOM	1283	O	LYS	C	293	9.021	52.081	16.925	1.00	25.35	8
ATOM	1284	N	ILE	C	294	9.502	52.769	14.834	1.00	23.01	7
ATOM	1285	CA	ILE	C	294	9.914	51.416	14.443	1.00	21.69	6
ATOM	1286	CB	ILE	C	294	10.149	51.365	12.898	1.00	20.45	6
ATOM	1287	CG2	ILE	C	294	10.902	50.053	12.595	1.00	22.39	6
ATOM	1288	CG1	ILE	C	294	8.826	51.424	12.182	1.00	22.59	6
ATOM	1289	CD1	ILE	C	294	9.013	51.723	10.682	1.00	22.71	6
ATOM	1290	C	ILE	C	294	11.139	50.978	15.210	1.00	21.79	6
ATOM	1291	O	ILE	C	294	11.250	49.852	15.725	1.00	23.79	8
ATOM	1292	N	ASP	C	295	12.098	51.912	15.441	1.00	23.67	7
ATOM	1293	CA	ASP	C	295	13.281	51.560	16.213	1.00	23.07	6
ATOM	1294	CB	ASP	C	295	14.291	52.722	16.301	1.00	27.78	6
ATOM	1295	CG	ASP	C	295	15.082	52.938	15.034	1.00	37.31	6
ATOM	1296	OD1	ASP	C	295	15.209	51.983	14.243	1.00	32.94	8
ATOM	1297	OD2	ASP	C	295	15.570	54.098	14.872	1.00	41.42	8
ATOM	1298	C	ASP	C	295	12.825	51.240	17.666	1.00	23.22	6
ATOM	1299	O	ASP	C	295	13.357	50.303	18.289	1.00	26.53	8
ATOM	1300	N	ASP	C	296	11.931	52.047	18.194	1.00	23.58	7
ATOM	1301	CA	ASP	C	296	11.458	51.889	19.570	1.00	23.39	6
ATOM	1302	CB	ASP	C	296	10.529	53.012	20.025	1.00	27.78	6
ATOM	1303	CG	ASP	C	296	11.224	54.362	20.124	1.00	29.71	6
ATOM	1304	OD1	ASP	C	296	12.461	54.427	20.176	1.00	31.37	8
ATOM	1305	OD2	ASP	C	296	10.444	55.326	20.197	1.00	39.13	8
ATOM	1306	C	ASP	C	296	10.756	50.552	19.733	1.00	27.01	6
ATOM	1307	O	ASP	C	296	10.850	49.914	20.794	1.00	29.39	8
ATOM	1308	N	LEU	C	297	10.007	50.102	18.742	1.00	23.26	7
ATOM	1309	CA	LEU	C	297	9.314	48.820	18.800	1.00	26.92	6
ATOM	1310	CB	LEU	C	297	8.515	48.599	17.481	1.00	23.50	6
ATOM	1311	CG	LEU	C	297	7.865	47.206	17.409	1.00	25.96	6
ATOM	1312	CD1	LEU	C	297	6.821	46.978	18.514	1.00	23.25	6
ATOM	1313	CD2	LEU	C	297	7.209	47.043	16.056	1.00	30.08	6
ATOM	1314	C	LEU	C	297	10.319	47.700	18.994	1.00	22.60	6
ATOM	1315	O	LEU	C	297	10.238	46.833	19.871	1.00	25.36	8
ATOM	1316	N	PHE	C	298	11.370	47.704	18.181	1.00	22.46	7
ATOM	1317	CA	PHE	C	298	12.397	46.657	18.190	1.00	22.98	6
ATOM	1318	CB	PHE	C	298	13.146	46.534	16.828	1.00	21.20	6
ATOM	1319	CG	PHE	C	298	12.215	45.936	15.763	1.00	21.65	6
ATOM	1320	CD1	PHE	C	298	11.603	46.775	14.851	1.00	23.88	6
ATOM	1321	CD2	PHE	C	298	11.945	44.579	15.727	1.00	19.61	6
ATOM	1322	CE1	PHE	C	298	10.711	46.287	13.918	1.00	23.10	6
ATOM	1323	CE2	PHE	C	298	10.976	44.082	14.879	1.00	22.89	6
ATOM	1324	CZ	PHE	C	298	10.385	44.944	13.954	1.00	22.89	6
ATOM	1325	C	PHE	C	298	13.346	46.765	19.366	1.00	22.24	6
ATOM	1326	O	PHE	C	298	13.995	45.762	19.696	1.00	26.14	8
ATOM	1327	N	SER	C	299	13.452	47.932	19.987	1.00	25.90	7
ATOM	1328	CA	SER	C	299	14.264	48.166	21.163	1.00	27.99	6
ATOM	1329	CB	SER	C	299	14.694	49.677	21.208	1.00	28.04	6
ATOM	1330	OG	SER	C	299	15.551	49.835	20.076	1.00	48.85	8
ATOM	1331	C	SER	C	299	13.465	47.944	22.441	1.00	27.66	6
ATOM	1332	O	SER	C	299	14.116	47.914	23.506	1.00	33.14	8
ATOM	1333	N	GLY	C	300	12.146	47.836	22.389	1.00	25.96	7
ATOM	1334	CA	GLY	C	300	11.389	47.595	23.618	1.00	26.90	6
ATOM	1335	C	GLY	C	300	11.182	48.875	24.404	1.00	30.76	6
ATOM	1336	O	GLY	C	300	11.023	48.830	25.639	1.00	31.00	8
ATOM	1337	N	LYS	C	301	11.073	49.975	23.685	1.00	29.45	7
ATOM	1338	CA	LYS	C	301	10.905	51.285	24.343	1.00	33.22	6
ATOM	1339	CB	LYS	C	301	12.104	52.130	23.800	1.00	34.54	6
ATOM	1340	CG	LYS	C	301	13.438	51.692	24.356	1.00	45.39	6
ATOM	1341	CD	LYS	C	301	14.579	52.509	23.760	1.00	55.89	6
ATOM	1342	CE	LYS	C	301	15.883	52.152	24.454	1.00	63.37	6
ATOM	1343	NZ	LYS	C	301	15.809	50.819	25.114	1.00	64.44	7
ATOM	1344	C	LYS	C	301	9.716	52.056	23.798	1.00	34.37	6
ATOM	1345	O	LYS	C	301	9.632	53.265	24.050	1.00	41.72	8
ATOM	1346	N	HIS	C	302	8.910	51.471	22.953	1.00	34.82	7
ATOM	1347	CA	HIS	C	302	7.804	52.130	22.291	1.00	37.17	6
ATOM	1348	CB	HIS	C	302	7.209	51.176	21.276	1.00	36.32	6
ATOM	1349	CG	HIS	C	302	6.061	51.594	20.444	1.00	49.41	6
ATOM	1350	CD2	HIS	C	302	5.233	52.660	20.480	1.00	59.81	6
ATOM	1351	ND1	HIS	C	302	5.644	50.821	19.377	1.00	48.06	7
ATOM	1352	CE1	HIS	C	302	4.594	51.386	18.808	1.00	59.89	6
ATOM	1353	NE2	HIS	C	302	4.330	52.514	19.455	1.00	63.35	7
ATOM	1354	C	HIS	C	302	6.748	52.610	23.267	1.00	38.73	6
ATOM	1355	O	HIS	C	302	6.229	51.770	24.028	1.00	38.79	8
ATOM	1356	OXT	HIS	C	302	6.450	53.825	23.192	1.00	50.99	8
ATOM	1357	OW	WAT	W	1	−4.224	33.423	34.144	1.00	53.27	8
ATOM	1358	OW	WAT	W	2	18.813	49.538	11.784	1.00	43.86	8
ATOM	1359	OW	WAT	W	3	18.261	39.681	10.865	1.00	39.76	8
ATOM	1360	OW	WAT	W	4	8.904	33.078	11.851	1.00	38.31	8
ATOM	1361	OW	WAT	W	5	4.199	60.972	19.377	1.00	52.52	8
ATOM	1362	OW	WAT	W	6	14.477	53.540	5.612	1.00	48.28	8
ATOM	1363	OW	WAT	W	7	11.280	35.102	−0.408	1.00	43.88	8
ATOM	1364	OW	WAT	W	8	10.087	32.358	34.001	1.00	39.96	8
ATOM	1365	OW	WAT	W	9	15.416	57.414	13.859	1.00	48.04	8
ATOM	1366	OW	WAT	W	10	1.929	52.862	20.272	1.00	55.69	8
ATOM	1367	OW	WAT	W	11	4.935	60.748	16.928	1.00	39.08	8
ATOM	1368	OW	WAT	W	12	−3.393	52.954	−1.588	1.00	50.38	8
ATOM	1369	OW	WAT	W	13	−13.253	36.368	20.479	1.00	42.42	8
ATOM	1370	OW	WAT	W	14	0.313	32.026	34.781	1.00	47.16	8
ATOM	1371	OW	WAT	W	15	−6.564	45.853	14.770	1.00	68.25	8
ATOM	1372	OW	WAT	W	16	12.038	51.785	0.724	1.00	41.22	8
ATOM	1373	OW	WAT	W	17	14.999	64.994	4.375	1.00	48.22	8
ATOM	1374	OW	WAT	W	18	17.970	48.546	24.089	1.00	68.67	8
ATOM	1375	OW	WAT	W	19	18.217	40.214	24.483	1.00	47.37	8
ATOM	1376	OW	WAT	W	20	1.939	28.873	14.169	1.00	44.69	8
ATOM	1377	OW	WAT	W	21	3.847	66.616	−1.008	1.00	44.63	8
ATOM	1378	OW	WAT	W	22	−3.915	63.084	7.867	1.00	45.45	8
ATOM	1379	OW	WAT	W	23	19.360	45.486	31.250	1.00	63.22	8
ATOM	1380	OW	WAT	W	24	10.025	47.358	30.471	1.00	67.04	8
ATOM	1381	OW	WAT	W	25	13.664	53.469	2.124	1.00	42.64	8
ATOM	1382	OW	WAT	W	26	−5.012	60.157	−2.193	1.00	61.60	8
ATOM	1383	OW	WAT	W	27	6.815	67.394	21.507	1.00	52.80	8
ATOM	1384	OW	WAT	W	28	17.915	33.402	34.758	1.00	44.35	8
ATOM	1385	OW	WAT	W	29	16.731	42.979	3.382	1.00	84.13	8
ATOM	1386	OW	WAT	W	30	−6.288	67.664	0.468	1.00	45.25	8
ATOM	1387	OW	WAT	W	31	7.402	62.280	10.335	1.00	42.54	8
ATOM	1388	OW	WAT	W	32	15.598	43.947	1.369	1.00	56.42	8
ATOM	1389	OW	WAT	W	33	−7.926	47.819	12.072	1.00	44.03	8
ATOM	1390	OW	WAT	W	34	16.998	49.958	15.318	1.00	48.80	8
ATOM	1391	OW	WAT	W	35	8.586	64.846	22.173	1.00	69.56	8
ATOM	1392	OW	WAT	W	36	−0.416	48.332	28.972	1.00	49.67	8
ATOM	1393	OW	WAT	W	37	−1.687	35.124	10.272	1.00	51.02	8
ATOM	1394	OW	WAT	W	38	8.930	32.323	14.635	1.00	43.76	8
ATOM	1395	OW	WAT	W	39	14.596	53.388	26.734	1.00	54.53	8
ATOM	1396	OW	WAT	W	40	−11.348	62.652	8.819	1.00	63.88	8
ATOM	1397	OW	WAT	W	41	3.903	62.050	15.465	1.00	38.48	8
ATOM	1398	OW	WAT	W	42	−7.252	41.756	19.850	1.00	52.81	8
ATOM	1399	OW	WAT	W	43	−1.996	56.577	17.341	1.00	59.40	8
ATOM	1400	OW	WAT	W	44	4.137	49.725	23.884	1.00	48.85	8
ATOM	1401	OW	WAT	W	45	15.737	51.416	6.167	1.00	38.54	8
ATOM	1402	OW	WAT	W	46	−5.011	40.117	20.046	1.00	38.42	8
ATOM	1403	OW	WAT	W	47	−13.873	33.451	19.673	1.00	42.16	8
ATOM	1404	OW	WAT	W	48	11.057	53.487	−1.251	1.00	51.34	8
ATOM	1405	OW	WAT	W	49	14.300	48.217	26.182	1.00	45.81	8
ATOM	1406	OW	WAT	W	50	12.120	58.997	−1.940	1.00	63.88	8
ATOM	1407	OW	WAT	W	51	−0.336	33.581	11.855	1.00	48.03	8
ATOM	1408	OW	WAT	W	52	16.829	63.174	4.226	1.00	48.59	8
ATOM	1409	OW	WAT	W	53	16.022	41.438	23.130	1.00	41.43	8
ATOM	1410	OW	WAT	W	54	−15.200	36.945	22.654	1.00	28.98	8
ATOM	1411	OW	WAT	W	55	13.277	40.851	6.595	1.00	29.49	8
ATOM	1412	OW	WAT	W	56	12.069	61.338	14.855	1.00	27.04	8
ATOM	1413	OW	WAT	W	57	3.227	32.023	23.771	1.00	30.91	8
ATOM	1414	OW	WAT	W	58	9.562	62.631	0.352	1.00	32.41	8
ATOM	1415	OW	WAT	W	59	6.585	69.144	1.589	1.00	39.21	8
ATOM	1416	OW	WAT	W	60	5.345	68.911	−0.882	1.00	44.18	8
ATOM	1417	OW	WAT	W	61	−0.751	50.368	19.292	1.00	32.73	8
ATOM	1418	OW	WAT	W	62	17.617	40.863	26.974	1.00	32.29	8
ATOM	1419	OW	WAT	W	63	1.179	39.116	32.520	1.00	34.20	8
ATOM	1420	OW	WAT	W	64	−3.110	37.236	22.171	1.00	33.88	8
ATOM	1421	OW	WAT	W	65	14.044	57.099	4.209	1.00	33.65	8
ATOM	1422	OW	WAT	W	66	15.989	40.653	9.396	1.00	30.96	8
ATOM	1423	OW	WAT	W	67	5.371	35.579	5.640	1.00	34.67	8
ATOM	1424	OW	WAT	W	68	−4.275	34.135	21.863	1.00	40.99	8
ATOM	1425	OW	WAT	W	69	−10.323	38.406	25.608	1.00	36.01	8
ATOM	1426	OW	WAT	W	70	−2.810	46.901	24.190	1.00	39.93	8
ATOM	1427	OW	WAT	W	71	13.870	64.852	12.989	1.00	34.39	8
ATOM	1428	OW	WAT	W	72	4.793	27.473	30.299	1.00	46.24	8
ATOM	1429	OW	WAT	W	73	−15.971	32.066	20.578	1.00	38.92	8
ATOM	1430	OW	WAT	W	74	5.399	34.420	8.086	1.00	39.29	8
ATOM	1431	OW	WAT	W	75	−0.519	32.450	14.342	1.00	33.68	8
ATOM	1432	OW	WAT	W	76	2.179	32.697	11.146	1.00	36.98	8
ATOM	1433	OW	WAT	W	77	10.170	56.080	−0.241	1.00	39.89	8
ATOM	1434	OW	WAT	W	78	5.714	48.333	1.212	1.00	37.11	8
ATOM	1435	OW	WAT	W	79	−4.290	33.857	16.226	1.00	37.36	8
ATOM	1436	OW	WAT	W	80	2.780	25.857	19.866	1.00	36.02	8
ATOM	1437	OW	WAT	W	81	12.798	43.202	2.474	1.00	34.74	8
ATOM	1438	OW	WAT	W	82	−7.897	39.332	18.472	1.00	41.75	8
ATOM	1439	OW	WAT	W	83	16.117	44.618	21.247	1.00	31.97	8
ATOM	1440	OW	WAT	W	84	11.055	65.023	0.596	1.00	38.11	8
ATOM	1441	OW	WAT	W	85	12.824	45.673	3.486	1.00	33.54	8
ATOM	1442	OW	WAT	W	86	15.100	60.207	1.681	1.00	45.21	8
ATOM	1443	OW	WAT	W	87	−4.960	50.919	0.707	1.00	47.99	8
ATOM	1444	OW	WAT	W	88	9.128	42.918	32.795	1.00	44.27	8
ATOM	1445	OW	WAT	W	89	9.762	58.054	20.187	1.00	47.67	8
ATOM	1446	OW	WAT	W	90	12.540	34.153	9.788	1.00	45.77	8
ATOM	1447	OW	WAT	W	91	17.905	51.635	10.678	1.00	40.67	8
ATOM	1448	OW	WAT	W	92	−3.398	39.623	8.128	1.00	45.41	8
ATOM	1449	OW	WAT	W	93	6.924	42.895	−0.650	1.00	42.91	8
ATOM	1450	OW	WAT	W	94	7.797	55.535	21.646	1.00	50.17	8
ATOM	1451	OW	WAT	W	95	12.822	64.411	2.584	1.00	37.53	8
ATOM	1452	OW	WAT	W	96	10.955	46.835	−5.508	1.00	45.36	8
ATOM	1453	OW	WAT	W	97	13.257	59.487	9.888	1.00	36.34	8
ATOM	1454	OW	WAT	W	98	14.865	39.030	19.548	1.00	41.41	8
ATOM	1455	OW	WAT	W	99	−2.138	41.902	25.462	1.00	41.60	8
ATOM	1456	OW	WAT	W	100	−3.706	31.806	24.679	1.00	40.94	8
ATOM	1457	OW	WAT	W	101	5.836	33.167	1.082	1.00	43.31	8
ATOM	1458	OW	WAT	W	102	23.483	39.507	35.275	1.00	57.98	8
ATOM	1459	OW	WAT	W	103	17.559	63.021	7.407	1.00	50.25	8
ATOM	1460	OW	WAT	W	104	19.056	43.139	28.930	1.00	42.00	8
ATOM	1461	OW	WAT	W	105	19.572	41.453	18.032	1.00	45.63	8
ATOM	1462	OW	WAT	W	106	6.525	39.243	−0.417	1.00	40.74	8
ATOM	1463	OW	WAT	W	107	3.627	31.518	12.831	1.00	38.63	8
ATOM	1464	OW	WAT	W	108	5.366	58.591	23.270	1.00	55.71	8
ATOM	1465	OW	WAT	W	109	−0.088	26.458	16.764	1.00	52.60	8
ATOM	1466	OW	WAT	W	110	17.119	48.571	−9.546	1.00	47.91	8
ATOM	1467	OW	WAT	W	111	1.096	44.692	2.583	1.00	40.04	8
ATOM	1468	OW	WAT	W	112	16.042	35.471	8.298	1.00	50.36	8
ATOM	1469	OW	WAT	W		113	12.648	35.159	33.701	1.00	39.34	8
ATOM	1470	OW	WAT	W	114	3.337	49.000	−0.094	1.00	52.85	8
ATOM	1471	OW	WAT	W	115	20.033	39.068	22.889	1.00	58.35	8
ATOM	1472	OW	WAT	W	116	10.097	47.403	34.472	1.00	58.00	8
ATOM	1473	OW	WAT	W	117	10.830	41.416	−3.209	1.00	41.27	8
ATOM	1474	OW	WAT	W	118	12.754	36.719	35.635	1.00	54.11	8
ATOM	1475	OW	WAT	W	119	−0.813	31.338	21.906	1.00	46.66	8
ATOM	1476	OW	WAT	W		120	3.965	25.061	22.618	1.00	44.72	8
ATOM	1477	OW	WAT	W	121	13.777	59.149	13.305	1.00	41.18	8
ATOM	1478	OW	WAT	W	122	4.277	55.533	20.931	1.00	46.53	8
ATOM	1479	OW	WAT	W	123	−7.345	30.636	20.890	1.00	46.01	8
ATOM	1480	OW	WAT	W	124	16.037	45.847	−5.475	1.00	50.06	8
ATOM	1481	OW	WAT	W	125	−3.061	47.338	18.259	1.00	41.61	8
ATOM	1482	OW	WAT	W	126	10.453	31.620	10.805	1.00	50.39	8
ATOM	1483	OW	WAT	W	127	17.496	40.971	20.796	1.00	55.25	8
ATOM	1484	OW	WAT	W	128	−6.207	32.805	19.155	1.00	58.66	8
ATOM	1485	OW	WAT	W	129	16.601	45.869	−1.260	1.00	59.55	8
ATOM	1486	OW	WAT	W		130	2.484	51.452	22.049	1.00	47.45	8
ATOM	1487	OW	WAT	W	131	11.516	67.657	23.120	1.00	55.77	8
ATOM	1488	OW	WAT	W	132	5.346	61.188	13.510	1.00	29.53	8
ATOM	1489	OW	WAT	W	133	13.484	40.850	3.961	1.00	38.04	8
ATOM	1490	OW	WAT	W	134	6.017	48.953	24.748	1.00	98.99	8
ATOM	1491	OW	WAT	W	135	12.715	45.073	31.090	1.00	47.26	8
ATOM	1492	OW	WAT	W	136	8.319	40.420	−2.773	1.00	47.04	8
ATOM	1493	OW	WAT	W	137	−8.731	32.859	33.302	1.00	49.10	8
ATOM	1494	OW	WAT	W	138	15.813	48.959	17.249	1.00	53.10	8
ATOM	1495	OW	WAT	W	139	−15.705	39.364	21.958	1.00	63.55	8
ATOM	1496	OW	WAT	W		140	−5.095	45.138	17.428	1.00	45.00	8
ATOM	1497	OW	WAT	W	141	−13.312	30.683	20.947	1.00	53.07	8
ATOM	1498	OW	WAT	W	142	−13.192	60.851	8.504	1.00	52.13	8
ATOM	1499	OW	WAT	W	143	23.328	40.686	16.795	1.00	47.26	8
ATOM	1500	OW	WAT	W	144	13.616	60.813	17.279	1.00	43.28	8
ATOM	1501	OW	WAT	W	145	12.017	47.329	−3.100	1.00	48.09	8
ATOM	1502	OW	WAT	W	146	10.595	61.299	−1.506	1.00	49.06	8
ATOM	1503	OW	WAT	W	147	8.027	61.147	−4.069	1.00	52.20	8
ATOM	1504	OW	WAT	W	148	−6.283	49.644	10.949	1.00	57.39	8
ATOM	1505	OW	WAT	W	149	−9.469	40.692	26.922	1.00	43.53	8
ATOM	1506	OW	WAT	W		150	19.210	50.226	21.171	1.00	58.41	8
ATOM	1507	OW	WAT	W	151	2.611	26.546	15.184	1.00	50.95	8
ATOM	1508	OW	WAT	W	152	3.965	46.489	−3.009	1.00	57.99	8
ATOM	1509	OW	WAT	W	153	16.271	55.882	11.030	1.00	48.24	8
ATOM	1510	OW	WAT	W	154	1.184	67.205	−1.174	1.00	47.38	8
ATOM	1511	OW	WAT	W	155	2.482	46.558	0.974	1.00	67.17	8
ATOM	1512	OW	WAT	W	156	11.027	55.889	23.958	1.00	54.67	8
ATOM	1513	OW	WAT	W	157	−4.446	30.923	22.181	1.00	62.18	8
ATOM	1514	OW	WAT	W	158	−3.844	44.313	24.890	1.00	42.34	8
ATOM	1515	OW	WAT	W	159	14.549	53.163	20.560	1.00	49.30	8
ATOM	1516	OW	WAT	W		160	−3.797	31.575	19.705	1.00	69.49	8
ATOM	1517	OW	WAT	W	161	6.756	25.504	17.575	1.00	49.43	8
ATOM	1518	OW	WAT	W	162	10.788	30.257	35.433	1.00	36.60	8
ATOM	1519	OW	WAT	W	163	21.237	50.223	9.133	1.00	56.25	8
ATOM	1520	OW	WAT	W	164	−6.177	45.663	3.966	1.00	58.49	8
ATOM	1521	OW	WAT	W	165	−1.644	33.990	22.144	1.00	32.61	8
ATOM	1522	OW	WAT	W	166	20.594	39.565	9.528	1.00	54.57	8
ATOM	1523	OW	WAT	W	167	15.964	59.646	9.793	1.00	50.70	8
ATOM	1524	OW	WAT	W	168	7.316	50.423	25.713	1.00	47.49	8
ATOM	1525	OW	WAT	W	169	23.295	32.789	15.200	1.00	57.39	8
ATOM	1526	OW	WAT	W		170	−6.898	46.350	20.730	1.00	50.13	8
ATOM	1527	OW	WAT	W	171	−8.760	52.976	−3.940	1.00	55.95	8
ATOM	1528	OW	WAT	W	172	−2.895	48.110	26.454	1.00	68.31	8
ATOM	1529	OW	WAT	W	173	−1.144	71.221	17.499	1.00	50.95	8
ATOM	1530	OW	WAT	W	174	12.604	56.338	22.115	1.00	55.77	8
ATOM	1531	OW	WAT	W	175	22.778	50.987	6.750	1.00	51.42	8
ATOM	1532	OW	WAT	W	176	9.430	60.647	−6.523	1.00	61.73	8
ATOM	1533	OW	WAT	W	177	15.767	60.697	14.713	1.00	61.57	8
ATOM	1534	OW	WAT	W	178	22.291	46.306	8.351	1.00	64.25	8
ATOM	1535	OW	WAT	W	179	14.393	57.247	1.565	1.00	50.53	8
ATOM	1536	OW	WAT	W		180	6.277	72.244	1.677	1.00	56.50	8
ATOM	1537	OW	WAT	W	181	−5.357	56.977	16.549	1.00	63.38	8
ATOM	1538	OW	WAT	W	182	20.252	47.811	25.759	1.00	59.54	8
ATOM	1539	OW	WAT	W	183	−0.767	65.909	−2.025	1.00	59.74	8
ATOM	1540	OW	WAT	W	184	8.023	52.581	−3.823	1.00	57.61	8
ATOM	1541	OW	WAT	W	185	22.973	31.298	13.186	1.00	61.46	8
ATOM	1542	OW	WAT	W	186	21.890	46.952	18.566	1.00	62.99	8
ATOM	1543	OW	WAT	W	187	12.545	56.301	−0.180	1.00	62.12	8
ATOM	1544	OW	WAT	W	188	0.899	33.958	8.083	1.00	52.91	8
ATOM	1545	OW	WAT	W	189	−4.871	46.670	29.841	1.00	66.19	8
ATOM	1546	OW	WAT	W	190	−1.898	31.738	34.170	1.00	52.17	8
ATOM	1547	OW	WAT	W	191	−1.189	41.151	2.866	1.00	53.86	8
ATOM	1548	OW	WAT	W	192	22.565	44.586	11.059	1.00	62.34	8
ATOM	1549	OW	WAT	W	193	−5.244	44.118	13.781	1.00	60.66	8
ATOM	1550	OW	WAT	W	194	5.422	49.607	−0.947	1.00	53.84	8
END

Claims (11)

1. A method for identifying a ligand for the large extracellular loop of CD81, comprising the steps of (a) providing a 3D structural representation of the large extracellular loop of CD81, wherein the 3D structural representation comprises a D helix having a residue Phe186, and wherein the 3D structural representation of the large extracellular loop of CD81 is set forth in the atomic co-ordinates of Table 1, or variants of the atomic co-ordinates of Table 1 thereof, in which the r.m.s. deviation of the x, y and z co-ordinates for all heavy atoms is less than 2.5 Å; (b) providing a 3D structural representation of a potential ligand; (c) using a computer to dock the 3D structural representation of the potential ligand with the 3D structural representation of the large extracellular loop of CD81 at a site comprising the residue Phe186, wherein a potential ligand that docks with the large extracellular loop of CD81 at the site comprising the residue Phe186 is identified as a ligand for the large extracellular loop of CD81; (d) contacting the ligand identified in step (c) with CD81 or a fragment thereof containing the large extracellular loop, and (e) assaying the interaction between the ligand and CD81 or the fragment thereof containing the large extracellular loop to determine whether the ligand identified in step (c) is a ligand for the large extracellular loop of CD81.

2. The method of claim 1, wherein using the computer to dock the 3D structural representations of the potential ligand with the 3D structural representation of the large extracellular loop of CD81 comprises geometric matching or minimising the energy of interaction between the ligand and the large extracellular loop of CD81.

3. The method of claim 2, wherein the step of using the computer to dock the potential ligand with the large extracellular loop of CD81 comprises screening members of a structural library of potential ligands to identify a ligand for CD81.

4. The method of claim 1, further comprising comparing the structures of the ligand identified in step (c), thereby defining a pharmacophore.

5. The method of claim 4, wherein the pharmacophore is used in de novo drug design.

6. The method of claim 1, wherein the 3D structural representation of the large extracellular loop of CD81 includes van der Waals contacts, electrostatic interactions, and/or hydrogen bonding opportunities on the CD81 surface.

7. The method of claim 1, wherein the site comprising the residue Phe186 further comprises one or more of Leu154, Thr163, Ile181, Ile182, Leu185, Glu188, and Asp196.

8. The method of claim 1, wherein the site comprising the residue Phe186 is the D-helix region Asn180-Phe186.

9. A method for identifying a ligand for the large extracellular loop of CD81, comprising:

(a) contacting a ligand with CD81 or a fragment thereof containing the large extracellular loop, and

(b) assaying the interaction between the ligand and CD81 or the fragment thereof containing the large extracellular loop to determine whether the ligand is a ligand for CD81,

wherein the ligand of step (a) was identified by a method comprising:

providing a 3D structural representation of the large extracellular loop of CD81, wherein the 3D structural representation comprises a D helix having a residue Phe186, and wherein the 3D structural representation of the large extracellular loop of CD81 is set forth in the atomic co-ordinates of Table 1, or variants of the atomic co-ordinates of Table 1, in which the r.m.s. deviation of the x, y and z co-ordinates for all heavy atoms is less than 2.5 Å;

providing a 3D structural representation of a potential ligand;

using a computer to dock the 3D structural representation of the potential ligand with the 3D structural representation of the large extracellular loop of CD81 at a site comprising the residue Phe186, wherein a potential ligand that docks with the large extracellular loop of CD81 at a site comprising the residue Phe186 is identified as a ligand for the large extracellular loop of CD81.

10. The method of claim 9, wherein the site comprising the residue Phe186 further comprises one or more of Leu154, Thr163, Ile181, Ile182, Leu185, Glu188, and Asp196.

11. The method of claim 9, wherein the site comprising the residue Phe186 is the D-helix region Asn180-Phe186.

Images